Datasets:

bigbio

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bionlp_st_2011_epi

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[ { "id": "PMID-12912907__text", "type": "abstract", "text": [ "HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. \nHypoxia-inducible factor (HIF), a transcriptional complex conserved from Caenorhabditis elegans to vertebrates, plays a pivotal role in cellular adaptation to low oxygen availability. In normoxia, the HIF-alpha subunits are targeted for destruction by prolyl hydroxylation, a specific modification that provides recognition for the E3 ubiquitin ligase complex containing the von Hippel-Lindau tumour suppressor protein (pVHL). Three HIF prolyl-hydroxylases (PHD1, 2 and 3) were identified recently in mammals and shown to hydroxylate HIF-alpha subunits. Here we show that specific 'silencing' of PHD2 with short interfering RNAs is sufficient to stabilize and activate HIF-1alpha in normoxia in all the human cells investigated. 'Silencing' of PHD1 and PHD3 has no effect on the stability of HIF-1alpha either in normoxia or upon re-oxygenation of cells briefly exposed to hypoxia. We therefore conclude that, in vivo, PHDs have distinct assigned functions, PHD2 being the critical oxygen sensor setting the low steady-state levels of HIF-1alpha in normoxia. Interestingly, PHD2 is upregulated by hypoxia, providing an HIF-1-dependent auto-regulatory mechanism driven by the oxygen tension.\n" ], "offsets": [ [ 0, 1301 ] ] } ]

[ { "id": "PMID-12912907_T1", "type": "Protein", "text": [ "HIF prolyl-hydroxylase 2" ], "offsets": [ [ 0, 24 ] ], "normalized": [] }, { "id": "PMID-12912907_T2", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 85, 95 ] ], "normalized": [] }, { "id": "PMID-12912907_T3", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 445, 454 ] ], "normalized": [] }, { "id": "PMID-12912907_T4", "type": "Protein", "text": [ "von Hippel-Lindau tumour suppressor" ], "offsets": [ [ 485, 520 ] ], "normalized": [] }, { "id": "PMID-12912907_T5", "type": "Protein", "text": [ "pVHL" ], "offsets": [ [ 530, 534 ] ], "normalized": [] }, { "id": "PMID-12912907_T6", "type": "Protein", "text": [ "PHD1" ], "offsets": [ [ 568, 572 ] ], "normalized": [] }, { "id": "PMID-12912907_T7", "type": "Protein", "text": [ "2" ], "offsets": [ [ 574, 575 ] ], "normalized": [] }, { "id": "PMID-12912907_T8", "type": "Protein", "text": [ "3" ], "offsets": [ [ 580, 581 ] ], "normalized": [] }, { "id": "PMID-12912907_T9", "type": "Protein", "text": [ "PHD2" ], "offsets": [ [ 706, 710 ] ], "normalized": [] }, { "id": "PMID-12912907_T10", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 779, 789 ] ], "normalized": [] }, { "id": "PMID-12912907_T11", "type": "Protein", "text": [ "PHD1" ], "offsets": [ [ 854, 858 ] ], "normalized": [] }, { "id": "PMID-12912907_T12", "type": "Protein", "text": [ "PHD3" ], "offsets": [ [ 863, 867 ] ], "normalized": [] }, { "id": "PMID-12912907_T13", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 902, 912 ] ], "normalized": [] }, { "id": "PMID-12912907_T14", "type": "Protein", "text": [ "PHD2" ], "offsets": [ [ 1068, 1072 ] ], "normalized": [] }, { "id": "PMID-12912907_T15", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1145, 1155 ] ], "normalized": [] }, { "id": "PMID-12912907_T16", "type": "Protein", "text": [ "PHD2" ], "offsets": [ [ 1184, 1188 ] ], "normalized": [] } ]

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[ { "id": "PMID-12912907_1", "entity_ids": [ "PMID-12912907_T4", "PMID-12912907_T5" ] } ]

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[ { "id": "PMID-12944473__text", "type": "abstract", "text": [ "Insulation of the chicken beta-globin chromosomal domain from a chromatin-condensing protein, MENT. \nActive genes are insulated from developmentally regulated chromatin condensation in terminally differentiated cells. We mapped the topography of a terminal stage-specific chromatin-condensing protein, MENT, across the active chicken beta-globin domain. We observed two sharp transitions of MENT concentration coinciding with the beta-globin boundary elements. The MENT distribution profile was opposite to that of acetylated core histones but correlated with that of histone H3 dimethylated at lysine 9 (H3me2K9). Ectopic MENT expression in NIH 3T3 cells caused a large-scale and specific remodeling of chromatin marked by H3me2K9. MENT colocalized with H3me2K9 both in chicken erythrocytes and NIH 3T3 cells. Mutational analysis of MENT and experiments with deacetylase inhibitors revealed the essential role of the reaction center loop domain and an inhibitory affect of histone hyperacetylation on the MENT-induced chromatin remodeling in vivo. In vitro, the elimination of the histone H3 N-terminal peptide containing lysine 9 by trypsin blocked chromatin self-association by MENT, while reconstitution with dimethylated but not acetylated N-terminal domain of histone H3 specifically restored chromatin self-association by MENT. We suggest that histone H3 modification at lysine 9 directly regulates chromatin condensation by recruiting MENT to chromatin in a fashion that is spatially constrained from active genes by gene boundary elements and histone hyperacetylation.\n" ], "offsets": [ [ 0, 1578 ] ] } ]

[ { "id": "PMID-12944473_T1", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 26, 37 ] ], "normalized": [] }, { "id": "PMID-12944473_T2", "type": "Protein", "text": [ "MENT" ], "offsets": [ [ 94, 98 ] ], "normalized": [] }, { "id": "PMID-12944473_T3", "type": "Protein", "text": [ "MENT" ], "offsets": [ [ 302, 306 ] ], "normalized": [] }, { "id": "PMID-12944473_T4", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 334, 345 ] ], "normalized": [] }, { "id": "PMID-12944473_T5", "type": "Protein", "text": [ "MENT" ], "offsets": [ [ 391, 395 ] ], "normalized": [] }, { "id": "PMID-12944473_T6", "type": "Protein", "text": [ "beta-globin" ], "offsets": [ [ 430, 441 ] ], "normalized": [] }, { "id": "PMID-12944473_T7", "type": "Protein", "text": [ "MENT" ], "offsets": [ [ 465, 469 ] ], "normalized": [] }, { "id": "PMID-12944473_T8", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 531, 539 ] ], "normalized": [] }, { "id": "PMID-12944473_T9", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 568, 578 ] ], "normalized": [] }, { "id": "PMID-12944473_T10", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 605, 607 ] ], "normalized": [] }, { "id": "PMID-12944473_T11", "type": "Protein", "text": [ "MENT" ], "offsets": [ [ 623, 627 ] ], "normalized": [] }, { "id": "PMID-12944473_T12", "type": "Protein", "text": [ "MENT" ], "offsets": [ [ 733, 737 ] ], "normalized": [] }, { "id": "PMID-12944473_T13", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 755, 757 ] ], "normalized": [] }, { "id": "PMID-12944473_T14", "type": "Protein", "text": [ "MENT" ], "offsets": [ [ 834, 838 ] ], "normalized": [] }, { "id": "PMID-12944473_T15", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 974, 981 ] ], "normalized": [] }, { "id": "PMID-12944473_T16", "type": "Protein", "text": [ "MENT" ], "offsets": [ [ 1006, 1010 ] ], "normalized": [] }, { "id": "PMID-12944473_T17", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 1082, 1092 ] ], "normalized": [] }, { "id": "PMID-12944473_T18", "type": "Protein", "text": [ "MENT" ], "offsets": [ [ 1181, 1185 ] ], "normalized": [] }, { "id": "PMID-12944473_T19", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 1266, 1276 ] ], "normalized": [] }, { "id": "PMID-12944473_T20", "type": "Protein", "text": [ "MENT" ], "offsets": [ [ 1329, 1333 ] ], "normalized": [] }, { "id": "PMID-12944473_T21", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 1351, 1361 ] ], "normalized": [] }, { "id": "PMID-12944473_T22", "type": "Protein", "text": [ "MENT" ], "offsets": [ [ 1443, 1447 ] ], "normalized": [] }, { "id": "PMID-12944473_T23", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1552, 1559 ] ], "normalized": [] }, { "id": "PMID-12944473_T26", "type": "Entity", "text": [ "lysine 9" ], "offsets": [ [ 595, 603 ] ], "normalized": [] }, { "id": "PMID-12944473_T27", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 610, 612 ] ], "normalized": [] }, { "id": "PMID-12944473_T31", "type": "Entity", "text": [ "N-terminal domain" ], "offsets": [ [ 1245, 1262 ] ], "normalized": [] } ]

[ { "id": "PMID-12944473_E1", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 515, 525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12944473_T8" } ] }, { "id": "PMID-12944473_E2", "type": "Methylation", "trigger": { "text": [ "dimethylated" ], "offsets": [ [ 579, 591 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12944473_T9" }, { "role": "Site", "ref_id": "PMID-12944473_T26" } ] }, { "id": "PMID-12944473_E3", "type": "Acetylation", "trigger": { "text": [ "hyperacetylation" ], "offsets": [ [ 982, 998 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12944473_T15" } ] }, { "id": "PMID-12944473_E4", "type": "Methylation", "trigger": { "text": [ "dimethylated" ], "offsets": [ [ 1213, 1225 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12944473_T19" }, { "role": "Site", "ref_id": "PMID-12944473_T31" } ] }, { "id": "PMID-12944473_E5", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 1234, 1244 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12944473_T19" }, { "role": "Site", "ref_id": "PMID-12944473_T31" } ] }, { "id": "PMID-12944473_E6", "type": "Acetylation", "trigger": { "text": [ "hyperacetylation" ], "offsets": [ [ 1560, 1576 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12944473_T23" } ] } ]

[ { "id": "PMID-12944473_1", "entity_ids": [ "PMID-12944473_T9", "PMID-12944473_T10" ] }, { "id": "PMID-12944473_2", "entity_ids": [ "PMID-12944473_T26", "PMID-12944473_T27" ] } ]

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[ { "id": "PMID-12960419__text", "type": "abstract", "text": [ "Requirement for neo1p in retrograde transport from the Golgi complex to the endoplasmic reticulum. \nNeo1p from Saccharomyces cerevisiae is an essential P-type ATPase and potential aminophospholipid translocase (flippase) in the Drs2p family. We have previously implicated Drs2p in protein transport steps in the late secretory pathway requiring ADP-ribosylation factor (ARF) and clathrin. Here, we present evidence that epitope-tagged Neo1p localizes to the endoplasmic reticulum (ER) and Golgi complex and is required for a retrograde transport pathway between these organelles. Using conditional alleles of NEO1, we find that loss of Neo1p function causes cargo-specific defects in anterograde protein transport early in the secretory pathway and perturbs glycosylation in the Golgi complex. Rer1-GFP, a protein that cycles between the ER and Golgi complex in COPI and COPII vesicles, is mislocalized to the vacuole in neo1-ts at the nonpermissive temperature. These phenotypes suggest that the anterograde protein transport defect is a secondary consequence of a defect in a COPI-dependent retrograde pathway. We propose that loss of lipid asymmetry in the cis Golgi perturbs retrograde protein transport to the ER.\n" ], "offsets": [ [ 0, 1219 ] ] } ]

[ { "id": "PMID-12960419_T1", "type": "Protein", "text": [ "neo1p" ], "offsets": [ [ 16, 21 ] ], "normalized": [] }, { "id": "PMID-12960419_T2", "type": "Protein", "text": [ "Neo1p" ], "offsets": [ [ 100, 105 ] ], "normalized": [] }, { "id": "PMID-12960419_T3", "type": "Protein", "text": [ "Drs2p" ], "offsets": [ [ 228, 233 ] ], "normalized": [] }, { "id": "PMID-12960419_T4", "type": "Protein", "text": [ "Drs2p" ], "offsets": [ [ 272, 277 ] ], "normalized": [] }, { "id": "PMID-12960419_T5", "type": "Protein", "text": [ "Neo1p" ], "offsets": [ [ 435, 440 ] ], "normalized": [] }, { "id": "PMID-12960419_T6", "type": "Protein", "text": [ "NEO1" ], "offsets": [ [ 609, 613 ] ], "normalized": [] }, { "id": "PMID-12960419_T7", "type": "Protein", "text": [ "Neo1p" ], "offsets": [ [ 636, 641 ] ], "normalized": [] }, { "id": "PMID-12960419_T8", "type": "Protein", "text": [ "Rer1" ], "offsets": [ [ 794, 798 ] ], "normalized": [] }, { "id": "PMID-12960419_T9", "type": "Protein", "text": [ "GFP" ], "offsets": [ [ 799, 802 ] ], "normalized": [] }, { "id": "PMID-12960419_T10", "type": "Protein", "text": [ "neo1" ], "offsets": [ [ 921, 925 ] ], "normalized": [] } ]

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[ { "id": "PMID-12966575__text", "type": "abstract", "text": [ "Fabrication of nickel and chromium nanoparticles using the protein cage of apoferritin. \nThe iron storage protein, apoferritin, has a cavity in which iron is oxidized and stored as a hydrated oxide core. The size of the core is about 7 nm in diameter and is regulated by the cavity size. The cavity can be utilized as a nanoreactor to grow inorganic crystals. We incubated apoferritin in nickel or chromium salt solutions to fabricate hydroxide nanoparticles in the cavity. By using a solution containing dissolved carbon dioxide and by precisely controlling the pH, we succeeded in fabricating nickel and chromium cores. During the hydroxylation process of nickel ions a large portion of the apoferritin precipitated through bulk precipitation of nickel hydroxide. Bulk precipitation was suppressed by adding ammonium ions. However, even in the presence of ammonium ions the core did not form using a degassed solution. We concluded that carbonate ions were indispensable for core formation and that the ammonium ions prevented precipitation in the bulk solution. The optimized condition for nickel core formation was 0.3 mg/mL horse spleen apoferritin and 5 mM ammonium nickel sulfate in water containing dissolved carbon dioxide. The pH was maintained at 8.65 using two buffer solutions: 150 mM HEPES (pH 7.5) and 195 mM CAPSO (pH 9.5) with 20 mM ammonium at 23 degrees C. The pH had not changed after 48 h. After 24 h of incubation, all apoferritins remained in the supernatant and all of them had cores. Recombinant L-ferritin showed less precipitation even above a pH of 8.65. A chromium core was formed under the following conditions: 0.1 mg/mL apoferritin, 1 mM ammonium chromium sulfate, 100 mM HEPES (pH 7.5) with a solution containing dissolved carbon dioxide. About 80% of the supernatant apoferritin (0.07 mg/mL) formed a core. In nickel and chromium core formation, carbonate ions would play an important role in accelerating the hydroxylation in the apoferritin cavity compared to the bulk solution outside.\n" ], "offsets": [ [ 0, 2023 ] ] } ]

[ { "id": "PMID-12966575_T1", "type": "Protein", "text": [ "L-ferritin" ], "offsets": [ [ 1521, 1531 ] ], "normalized": [] } ]

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[ { "id": "PMID-12972566__text", "type": "abstract", "text": [ "Histone hyperacetylation in mitosis prevents sister chromatid separation and produces chromosome segregation defects. \nPosttranslational modifications of core histones contribute to driving changes in chromatin conformation and compaction. Herein, we investigated the role of histone deacetylation on the mitotic process by inhibiting histone deacetylases shortly before mitosis in human primary fibroblasts. Cells entering mitosis with hyperacetylated histones displayed altered chromatin conformation associated with decreased reactivity to the anti-Ser 10 phospho H3 antibody, increased recruitment of protein phosphatase 1-delta on mitotic chromosomes, and depletion of heterochromatin protein 1 from the centromeric heterochromatin. Inhibition of histone deacetylation before mitosis produced defective chromosome condensation and impaired mitotic progression in living cells, suggesting that improper chromosome condensation may induce mitotic checkpoint activation. In situ hybridization analysis on anaphase cells demonstrated the presence of chromatin bridges, which were caused by persisting cohesion along sister chromatid arms after centromere separation. Thus, the presence of hyperacetylated chromatin during mitosis impairs proper chromosome condensation during the pre-anaphase stages, resulting in poor sister chromatid resolution. Lagging chromosomes consisting of single or paired sisters were also induced by the presence of hyperacetylated histones, indicating that the less constrained centromeric organization associated with heterochromatin protein 1 depletion may promote the attachment of kinetochores to microtubules coming from both poles.\n" ], "offsets": [ [ 0, 1668 ] ] } ]

[ { "id": "PMID-12972566_T1", "type": "Protein", "text": [ "Histone" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "PMID-12972566_T2", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 159, 167 ] ], "normalized": [] }, { "id": "PMID-12972566_T3", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 276, 283 ] ], "normalized": [] }, { "id": "PMID-12972566_T4", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 335, 342 ] ], "normalized": [] }, { "id": "PMID-12972566_T5", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 453, 461 ] ], "normalized": [] }, { "id": "PMID-12972566_T6", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 567, 569 ] ], "normalized": [] }, { "id": "PMID-12972566_T7", "type": "Protein", "text": [ "protein phosphatase 1-delta" ], "offsets": [ [ 605, 632 ] ], "normalized": [] }, { "id": "PMID-12972566_T8", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 752, 759 ] ], "normalized": [] }, { "id": "PMID-12972566_T9", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 1461, 1469 ] ], "normalized": [] } ]

[ { "id": "PMID-12972566_E1", "type": "Acetylation", "trigger": { "text": [ "hyperacetylation" ], "offsets": [ [ 8, 24 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12972566_T1" } ] }, { "id": "PMID-12972566_E2", "type": "Deacetylation", "trigger": { "text": [ "deacetylation" ], "offsets": [ [ 284, 297 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12972566_T3" } ] }, { "id": "PMID-12972566_E3", "type": "Acetylation", "trigger": { "text": [ "hyperacetylated" ], "offsets": [ [ 437, 452 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12972566_T5" } ] }, { "id": "PMID-12972566_E4", "type": "Deacetylation", "trigger": { "text": [ "deacetylation" ], "offsets": [ [ 760, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12972566_T8" } ] }, { "id": "PMID-12972566_E5", "type": "Acetylation", "trigger": { "text": [ "hyperacetylated" ], "offsets": [ [ 1445, 1460 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-12972566_T9" } ] } ]

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[ { "id": "PMID-1334619__text", "type": "abstract", "text": [ "Hydroxylated kininogens and kinins. \nHydroxyprolyl-3-bradykinin was identified in the digest of purified human high molecular weight (H) kininogen with plasma kallikrein. Hydroxyproline was not detected in the heavy and light chains portions of H kininogen, although they include three possible sites for hydroxylation of proline by proline hydroxylase. The content of hydroxyprolyl-3-bradykinin in H kininogen from individual plasmas varied from 14% to 64% of total kinin. The present results and our previous results indicate that only kinin moity in H kininogen from human and monkey plasmas has been partially hydroxylated post-translationally by proline-4-hydroxylase.\n" ], "offsets": [ [ 0, 674 ] ] } ]

[ { "id": "PMID-1334619_T1", "type": "Protein", "text": [ "kininogens" ], "offsets": [ [ 13, 23 ] ], "normalized": [] }, { "id": "PMID-1334619_T2", "type": "Protein", "text": [ "kinins" ], "offsets": [ [ 28, 34 ] ], "normalized": [] }, { "id": "PMID-1334619_T3", "type": "Protein", "text": [ "bradykinin" ], "offsets": [ [ 53, 63 ] ], "normalized": [] }, { "id": "PMID-1334619_T4", "type": "Protein", "text": [ "high molecular weight (H) kininogen" ], "offsets": [ [ 111, 146 ] ], "normalized": [] }, { "id": "PMID-1334619_T5", "type": "Protein", "text": [ "plasma kallikrein" ], "offsets": [ [ 152, 169 ] ], "normalized": [] }, { "id": "PMID-1334619_T6", "type": "Protein", "text": [ "H kininogen" ], "offsets": [ [ 245, 256 ] ], "normalized": [] }, { "id": "PMID-1334619_T7", "type": "Protein", "text": [ "bradykinin" ], "offsets": [ [ 385, 395 ] ], "normalized": [] }, { "id": "PMID-1334619_T8", "type": "Protein", "text": [ "H kininogen" ], "offsets": [ [ 399, 410 ] ], "normalized": [] }, { "id": "PMID-1334619_T9", "type": "Protein", "text": [ "kinin" ], "offsets": [ [ 467, 472 ] ], "normalized": [] }, { "id": "PMID-1334619_T10", "type": "Protein", "text": [ "kinin" ], "offsets": [ [ 538, 543 ] ], "normalized": [] }, { "id": "PMID-1334619_T11", "type": "Protein", "text": [ "H kininogen" ], "offsets": [ [ 553, 564 ] ], "normalized": [] } ]

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[ { "id": "PMID-1374224__text", "type": "abstract", "text": [ "Purification and characterization of soluble forms of human and rat stem cell factor recombinantly expressed by Escherichia coli and by Chinese hamster ovary cells. \nStem cell factor (SCF) is a novel, early-acting hematopoietic factor. It was isolated from the medium of a rat cell line in a soluble, processed form (Zsebo et al., 1990, Cell 63, 195). The cloned human and rat genes encode the soluble form plus additional C-terminal amino acids including a hydrophobic transmembrane domain (Martin et al., 1990, Cell 63, 203). We have recombinantly expressed forms of human and rat SCF corresponding to the soluble, processed form in Escherichia coli and in Chinese hamster ovary (CHO) cells. After expression in E. coli, folding and oxidation of the SCF polypeptides are required. The SCFs expressed in CHO cells are secreted into the medium in active state and, like the natural SCF, are glycosylated. Purification of the recombinant SCFs is described. Biological and biochemical characterization includes activity toward responsive human and mouse cell lines, N-terminal amino acid sequences, disulfide bond linkages, and sites of glycosylation.\n" ], "offsets": [ [ 0, 1150 ] ] } ]

[ { "id": "PMID-1374224_T1", "type": "Protein", "text": [ "stem cell factor" ], "offsets": [ [ 68, 84 ] ], "normalized": [] }, { "id": "PMID-1374224_T2", "type": "Protein", "text": [ "Stem cell factor" ], "offsets": [ [ 166, 182 ] ], "normalized": [] }, { "id": "PMID-1374224_T3", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 184, 187 ] ], "normalized": [] }, { "id": "PMID-1374224_T4", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 583, 586 ] ], "normalized": [] }, { "id": "PMID-1374224_T5", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 752, 755 ] ], "normalized": [] }, { "id": "PMID-1374224_T6", "type": "Protein", "text": [ "SCFs" ], "offsets": [ [ 787, 791 ] ], "normalized": [] }, { "id": "PMID-1374224_T7", "type": "Protein", "text": [ "SCF" ], "offsets": [ [ 882, 885 ] ], "normalized": [] }, { "id": "PMID-1374224_T8", "type": "Protein", "text": [ "SCFs" ], "offsets": [ [ 937, 941 ] ], "normalized": [] } ]

[ { "id": "PMID-1374224_E1", "type": "Glycosylation", "trigger": { "text": [ "glycosylated" ], "offsets": [ [ 891, 903 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1374224_T6" } ] } ]

[ { "id": "PMID-1374224_1", "entity_ids": [ "PMID-1374224_T2", "PMID-1374224_T3" ] } ]

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[ { "id": "PMID-1375279__text", "type": "abstract", "text": [ "Inhibition of fusion by neutralizing monoclonal antibodies to the haemagglutinin-neuraminidase glycoprotein of Newcastle disease virus. \nThe majority of neutralizing monoclonal antibodies (MAbs) to the haemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus prevent attachment of the virus to cellular receptors and inhibits virion-induced fusion from without (FFWO) and fusion from within (FFWI) mediated by the virus glycoprotein-laden infected cell surface. For these antibodies, the inhibition of fusion is presumed to be the result of the prevention of HN-mediated bridging of potential fusion partners. MAbs against antigenic sites 3 and 4 neutralize virus infectivity, but by a mechanism other than the prevention of attachment, the exact nature of which remains to be established. Antibodies to both of these sites effectively inhibit virion-induced FFWO, even when the inducing virus is not infectious. This is consistent with the mechanism of neutralization of these MAbs involving the inhibition of an early, post-attachment step in infection. MAbs to site 3 also inhibit FFWI, but those to site 4 do not, even when added at high concentrations. This suggests that the requirement for HN may be different in the two modes of fusion. The epitopes recognized by MAbs to sites 3 and 4 have been delineated by the identification of individual nucleotide substitutions in the HN genes of neutralization escape variants. Some of the deduced amino acid substitutions result in additional N-linked glycosylation sites in HN, which are utilized and presumably account for the escape from neutralization.\n" ], "offsets": [ [ 0, 1624 ] ] } ]

[ { "id": "PMID-1375279_T1", "type": "Protein", "text": [ "haemagglutinin-neuraminidase" ], "offsets": [ [ 66, 94 ] ], "normalized": [] }, { "id": "PMID-1375279_T2", "type": "Protein", "text": [ "haemagglutinin-neuraminidase" ], "offsets": [ [ 202, 230 ] ], "normalized": [] }, { "id": "PMID-1375279_T3", "type": "Protein", "text": [ "HN" ], "offsets": [ [ 232, 234 ] ], "normalized": [] }, { "id": "PMID-1375279_T4", "type": "Protein", "text": [ "HN" ], "offsets": [ [ 576, 578 ] ], "normalized": [] }, { "id": "PMID-1375279_T5", "type": "Protein", "text": [ "HN" ], "offsets": [ [ 1214, 1216 ] ], "normalized": [] }, { "id": "PMID-1375279_T6", "type": "Protein", "text": [ "HN" ], "offsets": [ [ 1400, 1402 ] ], "normalized": [] }, { "id": "PMID-1375279_T7", "type": "Protein", "text": [ "HN" ], "offsets": [ [ 1542, 1544 ] ], "normalized": [] }, { "id": "PMID-1375279_T8", "type": "Entity", "text": [ "N-linked glycosylation sites" ], "offsets": [ [ 1510, 1538 ] ], "normalized": [] } ]

[ { "id": "PMID-1375279_E1", "type": "Glycosylation", "trigger": { "text": [ "utilized" ], "offsets": [ [ 1556, 1564 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1375279_T7" }, { "role": "Site", "ref_id": "PMID-1375279_T8" } ] } ]

[ { "id": "PMID-1375279_1", "entity_ids": [ "PMID-1375279_T2", "PMID-1375279_T3" ] } ]

[]

[ { "id": "PMID-1381541__text", "type": "abstract", "text": [ "The influence of N-linked glycosylation on the antigenicity and immunogenicity of rubella virus E1 glycoprotein. \nRubella virus E1 glycoprotein contains three functional N-linked glycosylation sites. The role of N-linked glycosylation on the antigenicity and immunogenicity of E1 glycoprotein was studied using vaccinia recombinants expressing E1 glycosylation mutants. Expressed E1 glycosylation mutant proteins were recognized by a panel of E1-specific monoclonal antibodies in radioimmunoprecipitation, immunofluorescence, and immunoblotting, indicating that carbohydrate side chains on E1 are not involved in the constitution of epitopes recognized by these monoclonal antibodies. This observation was further supported by the fact that removal of oligosaccharides on E1 by glycosidase digestion did not significantly change the antigenicity of E1. All the glycosylation mutants were capable of eliciting anti-RV E1 antibodies. The single glycosylation mutants (G1, G2, and G3), but not the double mutant (G23) or the triple mutant (G123), were found to be capable of inducing virus neutralizing antibodies. Among the single glycosylation mutants, only G2 and G3 were active in producing hemagglutination inhibition antibodies in mice. Our findings suggest that although carbohydrate on E1 is not directly involved in the antigenic structures of E1, it is important in maintaining proper protein folding and stable conformation for expression of immunological epitopes on E1.\n" ], "offsets": [ [ 0, 1480 ] ] } ]

[ { "id": "PMID-1381541_T1", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 96, 98 ] ], "normalized": [] }, { "id": "PMID-1381541_T2", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 128, 130 ] ], "normalized": [] }, { "id": "PMID-1381541_T3", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 277, 279 ] ], "normalized": [] }, { "id": "PMID-1381541_T4", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 344, 346 ] ], "normalized": [] }, { "id": "PMID-1381541_T5", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 380, 382 ] ], "normalized": [] }, { "id": "PMID-1381541_T6", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 443, 445 ] ], "normalized": [] }, { "id": "PMID-1381541_T7", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 590, 592 ] ], "normalized": [] }, { "id": "PMID-1381541_T8", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 772, 774 ] ], "normalized": [] }, { "id": "PMID-1381541_T9", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 849, 851 ] ], "normalized": [] }, { "id": "PMID-1381541_T10", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 917, 919 ] ], "normalized": [] }, { "id": "PMID-1381541_T11", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 1291, 1293 ] ], "normalized": [] }, { "id": "PMID-1381541_T12", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 1350, 1352 ] ], "normalized": [] }, { "id": "PMID-1381541_T13", "type": "Protein", "text": [ "E1" ], "offsets": [ [ 1476, 1478 ] ], "normalized": [] } ]

[ { "id": "PMID-1381541_E1", "type": "Glycosylation", "trigger": { "text": [ "N-linked glycosylation" ], "offsets": [ [ 17, 39 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1381541_T1" } ] }, { "id": "PMID-1381541_E2", "type": "Glycosylation", "trigger": { "text": [ "N-linked glycosylation" ], "offsets": [ [ 212, 234 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1381541_T3" } ] } ]

[]

[]

[ { "id": "PMID-1420598__text", "type": "abstract", "text": [ "Glycosylation of the interleukin-1 receptor type I is required for optimal binding of interleukin-1. \nThe two types of cell surface receptors for interleukin-1 (IL-1) are glycoproteins that contain N-glycosidic chains on their extracellular portions. To determine the role of glycosylation of the IL-1 receptor type I (IL-1RtI) in the binding and function of IL-1, we used four plant lectins and glycosidase treatment on two different T-cell lines (EL4-6.1 and D10S) and expressing high number of binding sites for IL-1. The lectins wheat germ agglutinin, phytohemagglutinin, and concanavalin A inhibited in a dose-response manner the IL-1-induced proliferation of D10S cells. Binding of IL-1 was blocked and radioactive IL-1 was displaced from these cells by these lectins. Specific sugars (GlcNAc, NeuAc, Gal-GlcNAc-Man, Man, or alpha-MeMan) did not themselves affect IL-1 binding but reversed the blocking effects of the lectins. The two cell lines differed in their responses to the lectin-mediated inhibition of IL-1 binding. Digestion by N-glycosidase significantly decreased the capacity of cells to bind IL-1, and reduced by approximately 20,000 D the M(r) of the IL-1RtI. Neuraminidase and O-glycanase treatment did not alter the binding of IL-1 to D10S or EL4-6.1 cells. This study demonstrates that glycosylation of the extracellular domain of the IL-1RtI is due to N-linked carbohydrates, that the degree of glycosylation can vary in cells of different lineage, and that this N-linked glycosylation appears to be essential for optimal binding and activity of IL-1 to its type I receptor.\n" ], "offsets": [ [ 0, 1600 ] ] } ]

[ { "id": "PMID-1420598_T1", "type": "Protein", "text": [ "interleukin-1 receptor type I" ], "offsets": [ [ 21, 50 ] ], "normalized": [] }, { "id": "PMID-1420598_T2", "type": "Protein", "text": [ "IL-1 receptor type I" ], "offsets": [ [ 297, 317 ] ], "normalized": [] }, { "id": "PMID-1420598_T3", "type": "Protein", "text": [ "IL-1RtI" ], "offsets": [ [ 319, 326 ] ], "normalized": [] }, { "id": "PMID-1420598_T4", "type": "Protein", "text": [ "concanavalin A" ], "offsets": [ [ 580, 594 ] ], "normalized": [] }, { "id": "PMID-1420598_T5", "type": "Protein", "text": [ "IL-1RtI" ], "offsets": [ [ 1172, 1179 ] ], "normalized": [] }, { "id": "PMID-1420598_T6", "type": "Protein", "text": [ "IL-1RtI" ], "offsets": [ [ 1359, 1366 ] ], "normalized": [] }, { "id": "PMID-1420598_T10", "type": "Entity", "text": [ "carbohydrates" ], "offsets": [ [ 1386, 1399 ] ], "normalized": [] } ]

[ { "id": "PMID-1420598_E1", "type": "Glycosylation", "trigger": { "text": [ "Glycosylation" ], "offsets": [ [ 0, 13 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1420598_T1" } ] }, { "id": "PMID-1420598_E2", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 276, 289 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1420598_T2" } ] }, { "id": "PMID-1420598_E3", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 1310, 1323 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1420598_T6" }, { "role": "Sidechain", "ref_id": "PMID-1420598_T10" } ] }, { "id": "PMID-1420598_E4", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 1420, 1433 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1420598_T6" } ] }, { "id": "PMID-1420598_E5", "type": "Glycosylation", "trigger": { "text": [ "N-linked glycosylation" ], "offsets": [ [ 1488, 1510 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1420598_T6" } ] } ]

[ { "id": "PMID-1420598_1", "entity_ids": [ "PMID-1420598_T2", "PMID-1420598_T3" ] } ]

[]

[ { "id": "PMID-14500524__text", "type": "abstract", "text": [ "Expression of Cpgp40/15 in Toxoplasma gondii: a surrogate system for the study of Cryptosporidium glycoprotein antigens. \nCryptosporidium parvum is a waterborne enteric coccidian that causes diarrheal disease in a wide range of hosts. Development of successful therapies is hampered by the inability to culture the parasite and the lack of a transfection system for genetic manipulation. The glycoprotein products of the Cpgp40/15 gene, gp40 and gp15, are involved in C. parvum sporozoite attachment to and invasion of host cells and, as such, may be good targets for anticryptosporidial therapies. However, the function of these antigens appears to be dependent on the presence of multiple O-linked alpha-N-acetylgalactosamine (alpha-GalNAc) determinants. A eukaryotic expression system that would produce proteins bearing glycosylation patterns similar to those found on the native C. parvum glycoproteins would greatly facilitate the molecular and functional characterization of these antigens. As a unique approach to this problem, the Cpgp40/15 gene was transiently expressed in Toxoplasma gondii, and the expressed recombinant glycoproteins were characterized. Antisera to gp40 and gp15 reacted with the surface membranes of tachyzoites expressing the Cpgp40/15 construct, and this reactivity colocalized with that of antiserum to the T. gondii surface protein SAG1. Surface membrane localization was dependent on the presence of the glycophosphatidylinositol anchor attachment site present in the gp15 coding sequence. The presence of terminal O-linked alpha-GalNAc determinants on the T. gondii recombinant gp40 was confirmed by reactivity with Helix pomatia lectin and the monoclonal antibody 4E9, which recognizes alpha-GalNAc residues, and digestion with alpha-N-acetylgalactosaminidase. In addition to appropriate localization and glycosylation, T. gondii apparently processes the gp40/15 precursor into the gp40 and gp15 component glycopolypeptides, albeit inefficiently. These results suggest that a surrogate system using T. gondii for the study of Cryptosporidium biology may be useful.\n" ], "offsets": [ [ 0, 2103 ] ] } ]

[ { "id": "PMID-14500524_T1", "type": "Protein", "text": [ "Cpgp40/15" ], "offsets": [ [ 14, 23 ] ], "normalized": [] }, { "id": "PMID-14500524_T2", "type": "Protein", "text": [ "Cpgp40/15" ], "offsets": [ [ 421, 430 ] ], "normalized": [] }, { "id": "PMID-14500524_T3", "type": "Protein", "text": [ "gp40" ], "offsets": [ [ 437, 441 ] ], "normalized": [] }, { "id": "PMID-14500524_T4", "type": "Protein", "text": [ "gp15" ], "offsets": [ [ 446, 450 ] ], "normalized": [] }, { "id": "PMID-14500524_T5", "type": "Protein", "text": [ "Cpgp40/15" ], "offsets": [ [ 1040, 1049 ] ], "normalized": [] }, { "id": "PMID-14500524_T6", "type": "Protein", "text": [ "gp40" ], "offsets": [ [ 1179, 1183 ] ], "normalized": [] }, { "id": "PMID-14500524_T7", "type": "Protein", "text": [ "gp15" ], "offsets": [ [ 1188, 1192 ] ], "normalized": [] }, { "id": "PMID-14500524_T8", "type": "Protein", "text": [ "Cpgp40/15" ], "offsets": [ [ 1258, 1267 ] ], "normalized": [] }, { "id": "PMID-14500524_T9", "type": "Protein", "text": [ "SAG1" ], "offsets": [ [ 1367, 1371 ] ], "normalized": [] }, { "id": "PMID-14500524_T10", "type": "Protein", "text": [ "gp15" ], "offsets": [ [ 1504, 1508 ] ], "normalized": [] }, { "id": "PMID-14500524_T11", "type": "Protein", "text": [ "gp40" ], "offsets": [ [ 1615, 1619 ] ], "normalized": [] }, { "id": "PMID-14500524_T12", "type": "Protein", "text": [ "gp40/15" ], "offsets": [ [ 1893, 1900 ] ], "normalized": [] }, { "id": "PMID-14500524_T13", "type": "Protein", "text": [ "gp40" ], "offsets": [ [ 1920, 1924 ] ], "normalized": [] }, { "id": "PMID-14500524_T14", "type": "Protein", "text": [ "gp15" ], "offsets": [ [ 1929, 1933 ] ], "normalized": [] }, { "id": "PMID-14500524_T16", "type": "Entity", "text": [ "alpha-N-acetylgalactosamine" ], "offsets": [ [ 700, 727 ] ], "normalized": [] }, { "id": "PMID-14500524_T17", "type": "Entity", "text": [ "alpha-GalNAc" ], "offsets": [ [ 729, 741 ] ], "normalized": [] }, { "id": "PMID-14500524_T19", "type": "Entity", "text": [ "alpha-GalNAc" ], "offsets": [ [ 1560, 1572 ] ], "normalized": [] } ]

[ { "id": "PMID-14500524_E1", "type": "Glycosylation", "trigger": { "text": [ "O-linked" ], "offsets": [ [ 691, 699 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14500524_T3" }, { "role": "Sidechain", "ref_id": "PMID-14500524_T16" } ] }, { "id": "PMID-14500524_E2", "type": "Glycosylation", "trigger": { "text": [ "O-linked" ], "offsets": [ [ 691, 699 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14500524_T4" }, { "role": "Sidechain", "ref_id": "PMID-14500524_T16" } ] }, { "id": "PMID-14500524_E3", "type": "Glycosylation", "trigger": { "text": [ "O-linked" ], "offsets": [ [ 1551, 1559 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14500524_T11" }, { "role": "Sidechain", "ref_id": "PMID-14500524_T19" } ] } ]

[ { "id": "PMID-14500524_1", "entity_ids": [ "PMID-14500524_T16", "PMID-14500524_T17" ] } ]

[]

[ { "id": "PMID-14504087__text", "type": "abstract", "text": [ "Aberrant methylation of DAP-kinase in therapy-related acute myeloid leukemia and myelodysplastic syndromes. \nDeath-associated protein kinase (DAP-kinase), a proapoptotic serine/threonine kinase, is a candidate tumor suppressor gene. We studied the methylation status of DAP-kinase of 194 bone marrow samples from 160 patients with acute myeloid leukemia (AML) and 34 with a myelodysplastic syndrome (MDS) at the time of initial diagnosis by polymerase chain reaction (PCR). Hypermethylation of DAP-kinase was present in 27.5% (44 of 160) of AML and in 47% (16 of 34) of MDS specimens and significantly correlated to loss of DAP-kinase expression (P =.008). It was significantly more frequent in AML secondary to therapy for other malignancies (s-AML; 14 of 29, 48.3%), as compared to de novo AML (30 of 131, 22.9%, P =.01). DAP-kinase hypermethylation in AML was associated with myelodysplastic changes in the bone marrow at the time of the initial diagnosis (P =.002) and with the presence of cytogenetic abnormalities (P =.02). Alteration in the apoptotic response due to the loss of DAP-kinase function may be an early event in the transformation pathway to secondary leukemia via myelodysplasia.\n" ], "offsets": [ [ 0, 1200 ] ] } ]

[ { "id": "PMID-14504087_T1", "type": "Protein", "text": [ "DAP-kinase" ], "offsets": [ [ 24, 34 ] ], "normalized": [] }, { "id": "PMID-14504087_T2", "type": "Protein", "text": [ "Death-associated protein kinase" ], "offsets": [ [ 109, 140 ] ], "normalized": [] }, { "id": "PMID-14504087_T3", "type": "Protein", "text": [ "DAP-kinase" ], "offsets": [ [ 142, 152 ] ], "normalized": [] }, { "id": "PMID-14504087_T4", "type": "Protein", "text": [ "DAP-kinase" ], "offsets": [ [ 270, 280 ] ], "normalized": [] }, { "id": "PMID-14504087_T5", "type": "Protein", "text": [ "DAP-kinase" ], "offsets": [ [ 494, 504 ] ], "normalized": [] }, { "id": "PMID-14504087_T6", "type": "Protein", "text": [ "DAP-kinase" ], "offsets": [ [ 824, 834 ] ], "normalized": [] }, { "id": "PMID-14504087_T7", "type": "Protein", "text": [ "DAP-kinase" ], "offsets": [ [ 1086, 1096 ] ], "normalized": [] } ]

[ { "id": "PMID-14504087_E1", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 9, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14504087_T1" } ] }, { "id": "PMID-14504087_E2", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 248, 259 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14504087_T4" } ] }, { "id": "PMID-14504087_E3", "type": "DNA_methylation", "trigger": { "text": [ "Hypermethylation" ], "offsets": [ [ 474, 490 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14504087_T5" } ] }, { "id": "PMID-14504087_E4", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylation" ], "offsets": [ [ 835, 851 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14504087_T6" } ] } ]

[ { "id": "PMID-14504087_1", "entity_ids": [ "PMID-14504087_T2", "PMID-14504087_T3" ] } ]

[]

[ { "id": "PMID-14506639__text", "type": "abstract", "text": [ "Molecular pathology of atypical polypoid adenomyoma of the uterus. \nAtypical polypoid adenomyoma (APA) is an uncommon and benign tumor of the uterus. In some patients, however, APA has been found to coexist with or to precede the development of an endometrioid adenocarcinoma similarly to complex endometrial hyperplasia. The molecular changes underlying the progression from APA to adenocarcinoma are unknown. DNA from paraffin-embedded tissue of 6 APAs was evaluated for microsatellite instability (MI), MLH-1 promoter hypermethylation, and CTNNB-1 mutations. Tissue sections were also subjected to MLH-1, MSH-2, and beta-catenin immunostaining. MI was not detected in any case. Two tumors exhibited MLH-1 promoter hypermethylation and showed focal negative MHL-1 immunostaining; 1 of these showed marked architectural complexity and cellular pleomorphism. Five cases presented beta-catenin nuclear immunoreactivity, but none of them had CTNNB-1 mutations. The results of this study suggest that APA and complex endometrial hyperplasia may share some molecular alterations. Some APAs exhibit MLH-1 promoter hypermethylation with focal lack of MLH-1 immunostaining, a molecular abnormality involved in the transition from complex atypical hyperplasia to endometrioid adenocarcinoma.\n" ], "offsets": [ [ 0, 1284 ] ] } ]

[ { "id": "PMID-14506639_T1", "type": "Protein", "text": [ "MLH-1" ], "offsets": [ [ 506, 511 ] ], "normalized": [] }, { "id": "PMID-14506639_T2", "type": "Protein", "text": [ "CTNNB-1" ], "offsets": [ [ 543, 550 ] ], "normalized": [] }, { "id": "PMID-14506639_T3", "type": "Protein", "text": [ "MLH-1" ], "offsets": [ [ 601, 606 ] ], "normalized": [] }, { "id": "PMID-14506639_T4", "type": "Protein", "text": [ "MSH-2" ], "offsets": [ [ 608, 613 ] ], "normalized": [] }, { "id": "PMID-14506639_T5", "type": "Protein", "text": [ "beta-catenin" ], "offsets": [ [ 619, 631 ] ], "normalized": [] }, { "id": "PMID-14506639_T6", "type": "Protein", "text": [ "MLH-1" ], "offsets": [ [ 702, 707 ] ], "normalized": [] }, { "id": "PMID-14506639_T7", "type": "Protein", "text": [ "beta-catenin" ], "offsets": [ [ 880, 892 ] ], "normalized": [] }, { "id": "PMID-14506639_T8", "type": "Protein", "text": [ "CTNNB-1" ], "offsets": [ [ 940, 947 ] ], "normalized": [] }, { "id": "PMID-14506639_T9", "type": "Protein", "text": [ "MLH-1" ], "offsets": [ [ 1094, 1099 ] ], "normalized": [] }, { "id": "PMID-14506639_T10", "type": "Protein", "text": [ "MLH-1" ], "offsets": [ [ 1145, 1150 ] ], "normalized": [] }, { "id": "PMID-14506639_T11", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 512, 520 ] ], "normalized": [] }, { "id": "PMID-14506639_T13", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 708, 716 ] ], "normalized": [] }, { "id": "PMID-14506639_T15", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1100, 1108 ] ], "normalized": [] } ]

[ { "id": "PMID-14506639_E1", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylation" ], "offsets": [ [ 521, 537 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14506639_T1" }, { "role": "Site", "ref_id": "PMID-14506639_T11" } ] }, { "id": "PMID-14506639_E2", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylation" ], "offsets": [ [ 717, 733 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14506639_T6" }, { "role": "Site", "ref_id": "PMID-14506639_T13" } ] }, { "id": "PMID-14506639_E3", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylation" ], "offsets": [ [ 1109, 1125 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14506639_T9" }, { "role": "Site", "ref_id": "PMID-14506639_T15" } ] } ]

[]

[]

[ { "id": "PMID-14521712__text", "type": "abstract", "text": [ "A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation. \nBACKGROUND: The hypoxia-inducible factor (HIF) transcription complex, which is activated by low oxygen tension, controls a diverse range of cellular processes including angiogenesis and erythropoiesis. Under normoxic conditions, the alpha subunit of HIF is rapidly degraded in a manner dependent on hydroxylation of two conserved proline residues at positions 402 and 564 in HIF-1alpha in the oxygen-dependent degradation (ODD) domain. This allows subsequent recognition by the von Hippel-Lindau (VHL) tumor suppressor protein, which targets HIF for degradation by the ubiquitin-proteasome pathway. Under hypoxic conditions, prolyl hydroxylation of HIF is inhibited, allowing it to escape VHL-mediated degradation. The transcriptional regulation of the erythropoietin gene by HIF raises the possibility that HIF may play a role in disorders of erythropoiesis, such as idiopathic erythrocytosis (IE). RESULTS: Patients with IE were screened for changes in the HIF-1alpha coding sequence, and a change in the ODD domain that converts Pro-582 to Ser was identified in several patients. This same change, however, was also detected at a significant frequency, 0.073, in unaffected controls compared to 0.109 in the IE patient group. In vitro hydroxylation assays examining this amino acid change failed to reveal a discernible effect on HIF hydroxylation at Pro-564. CONCLUSION: The Pro582Ser change represents a common polymorphism of HIF-1alpha that does not impair HIF-1alpha prolyl hydroxylation. Although the Pro582Ser polymorphism is located in the ODD domain of HIF-1alpha it does not diminish the association of HIF-1alpha with VHL. Thus, it is unlikely that this polymorphism accounts for the erythrocytosis in the group of IE patients studied.\n" ], "offsets": [ [ 0, 1909 ] ] } ]

[ { "id": "PMID-14521712_T1", "type": "Protein", "text": [ "hypoxia inducible factor-1alpha" ], "offsets": [ [ 74, 105 ] ], "normalized": [] }, { "id": "PMID-14521712_T2", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 107, 117 ] ], "normalized": [] }, { "id": "PMID-14521712_T3", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 534, 544 ] ], "normalized": [] }, { "id": "PMID-14521712_T4", "type": "Protein", "text": [ "von Hippel-Lindau (VHL) tumor suppressor" ], "offsets": [ [ 637, 677 ] ], "normalized": [] }, { "id": "PMID-14521712_T5", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 728, 737 ] ], "normalized": [] }, { "id": "PMID-14521712_T6", "type": "Protein", "text": [ "erythropoietin" ], "offsets": [ [ 912, 926 ] ], "normalized": [] }, { "id": "PMID-14521712_T7", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1118, 1128 ] ], "normalized": [] }, { "id": "PMID-14521712_T8", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1591, 1601 ] ], "normalized": [] }, { "id": "PMID-14521712_T9", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1623, 1633 ] ], "normalized": [] }, { "id": "PMID-14521712_T10", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1724, 1734 ] ], "normalized": [] }, { "id": "PMID-14521712_T11", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1775, 1785 ] ], "normalized": [] }, { "id": "PMID-14521712_T12", "type": "Protein", "text": [ "VHL" ], "offsets": [ [ 1791, 1794 ] ], "normalized": [] }, { "id": "PMID-14521712_T13", "type": "Entity", "text": [ "Pro-564" ], "offsets": [ [ 135, 142 ] ], "normalized": [] }, { "id": "PMID-14521712_T16", "type": "Entity", "text": [ "proline residues" ], "offsets": [ [ 489, 505 ] ], "normalized": [] }, { "id": "PMID-14521712_T17", "type": "Entity", "text": [ "prolyl" ], "offsets": [ [ 1634, 1640 ] ], "normalized": [] } ]

[ { "id": "PMID-14521712_E1", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 143, 156 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14521712_T1" }, { "role": "Site", "ref_id": "PMID-14521712_T13" } ] }, { "id": "PMID-14521712_E2", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 458, 471 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14521712_T3" }, { "role": "Site", "ref_id": "PMID-14521712_T16" } ] }, { "id": "PMID-14521712_E3", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 1641, 1654 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14521712_T9" }, { "role": "Site", "ref_id": "PMID-14521712_T17" } ] } ]

[ { "id": "PMID-14521712_1", "entity_ids": [ "PMID-14521712_T1", "PMID-14521712_T2" ] } ]

[]

[ { "id": "PMID-14521911__text", "type": "abstract", "text": [ "Expression of histone acetyltransferases was down-regulated in poly(ADP-ribose) polymerase-1-deficient murine cells. \nNF-kappaB-dependent, as well as human immunodeficiency virus type-1 (HIV-1) long terminal repeat (LTR)-dependent, reporter gene expression was significantly impaired in cells derived from poly(ADP-ribose) polymerase-1 (PARP-1)-knockout (PARP-1 -/-) mice. In addition, the level of protein acetylation was markedly lower in PARP-1 -/- cells than control (PARP-1 +/+) cells. Surprisingly, the expression levels of histone acetyltransferases (HATs), p300, cAMP response element-binding protein-binding protein (CBP), and p300/CBP-associated factor (PCAF), were significantly reduced in PARP-1 -/- cells, as compared with PARP-1 +/+ cells. These results suggest that PARP-1 is required for the proper expression of particular HATs. Since p300 and CBP are coactivators of NF-kappaB, we propose here that PARP-1 participates in NF-kappaB-dependent transcription by means of maintaining the expression of HATs.\n" ], "offsets": [ [ 0, 1022 ] ] } ]

[ { "id": "PMID-14521911_T1", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 14, 21 ] ], "normalized": [] }, { "id": "PMID-14521911_T2", "type": "Protein", "text": [ "poly(ADP-ribose) polymerase-1" ], "offsets": [ [ 63, 92 ] ], "normalized": [] }, { "id": "PMID-14521911_T3", "type": "Protein", "text": [ "poly(ADP-ribose) polymerase-1" ], "offsets": [ [ 306, 335 ] ], "normalized": [] }, { "id": "PMID-14521911_T4", "type": "Protein", "text": [ "PARP-1" ], "offsets": [ [ 337, 343 ] ], "normalized": [] }, { "id": "PMID-14521911_T5", "type": "Protein", "text": [ "PARP-1" ], "offsets": [ [ 355, 361 ] ], "normalized": [] }, { "id": "PMID-14521911_T6", "type": "Protein", "text": [ "PARP-1" ], "offsets": [ [ 441, 447 ] ], "normalized": [] }, { "id": "PMID-14521911_T7", "type": "Protein", "text": [ "PARP-1" ], "offsets": [ [ 472, 478 ] ], "normalized": [] }, { "id": "PMID-14521911_T8", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 530, 537 ] ], "normalized": [] }, { "id": "PMID-14521911_T9", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 565, 569 ] ], "normalized": [] }, { "id": "PMID-14521911_T10", "type": "Protein", "text": [ "cAMP response element-binding protein-binding protein" ], "offsets": [ [ 571, 624 ] ], "normalized": [] }, { "id": "PMID-14521911_T11", "type": "Protein", "text": [ "CBP" ], "offsets": [ [ 626, 629 ] ], "normalized": [] }, { "id": "PMID-14521911_T12", "type": "Protein", "text": [ "p300/CBP-associated factor" ], "offsets": [ [ 636, 662 ] ], "normalized": [] }, { "id": "PMID-14521911_T13", "type": "Protein", "text": [ "PCAF" ], "offsets": [ [ 664, 668 ] ], "normalized": [] }, { "id": "PMID-14521911_T14", "type": "Protein", "text": [ "PARP-1" ], "offsets": [ [ 701, 707 ] ], "normalized": [] }, { "id": "PMID-14521911_T15", "type": "Protein", "text": [ "PARP-1" ], "offsets": [ [ 736, 742 ] ], "normalized": [] }, { "id": "PMID-14521911_T16", "type": "Protein", "text": [ "PARP-1" ], "offsets": [ [ 781, 787 ] ], "normalized": [] }, { "id": "PMID-14521911_T17", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 852, 856 ] ], "normalized": [] }, { "id": "PMID-14521911_T18", "type": "Protein", "text": [ "CBP" ], "offsets": [ [ 861, 864 ] ], "normalized": [] }, { "id": "PMID-14521911_T19", "type": "Protein", "text": [ "PARP-1" ], "offsets": [ [ 917, 923 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-14521911_1", "entity_ids": [ "PMID-14521911_T3", "PMID-14521911_T4" ] }, { "id": "PMID-14521911_2", "entity_ids": [ "PMID-14521911_T10", "PMID-14521911_T11" ] }, { "id": "PMID-14521911_3", "entity_ids": [ "PMID-14521911_T12", "PMID-14521911_T13" ] } ]

[]

[ { "id": "PMID-14550269__text", "type": "abstract", "text": [ "The ITIM-bearing CLECSF6 (DCIR) is down-modulated in neutrophils by neutrophil activating agents. \nThe recently discovered CLECSF6 protein displays the features of a receptor involved in the down-modulation of leukocyte activation. Although CLECSF6 has been the focus of the interest of many researchers lately, a Western blot characterization of the protein is still lacking. This highly reduces our ability to gain full knowledge of the biological relevance of this protein in cell responses. We produced two rabbit polyclonal antisera that detected a glycosylated protein at approximately 35kDa in neutrophils. Four different CLECSF6 mRNA species have been discovered to date. When deglycosylated, the protein displayed the molecular weight expected for the longest CLECSF6 form. Neutrophil membrane fractions were strongly enriched in the protein. We showed a down-modulation of the expression of this protein in neutrophils treated with granulocyte-macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF-alpha), lipopolysaccharide (LPS), and interleukin (IL)-4. This work supports the hypothesis that CLECSF6 is involved in the control of inflammation in neutrophils.\n" ], "offsets": [ [ 0, 1192 ] ] } ]

[ { "id": "PMID-14550269_T1", "type": "Protein", "text": [ "CLECSF6" ], "offsets": [ [ 17, 24 ] ], "normalized": [] }, { "id": "PMID-14550269_T2", "type": "Protein", "text": [ "DCIR" ], "offsets": [ [ 26, 30 ] ], "normalized": [] }, { "id": "PMID-14550269_T3", "type": "Protein", "text": [ "CLECSF6" ], "offsets": [ [ 123, 130 ] ], "normalized": [] }, { "id": "PMID-14550269_T4", "type": "Protein", "text": [ "CLECSF6" ], "offsets": [ [ 241, 248 ] ], "normalized": [] }, { "id": "PMID-14550269_T5", "type": "Protein", "text": [ "CLECSF6" ], "offsets": [ [ 629, 636 ] ], "normalized": [] }, { "id": "PMID-14550269_T6", "type": "Protein", "text": [ "CLECSF6" ], "offsets": [ [ 769, 776 ] ], "normalized": [] }, { "id": "PMID-14550269_T7", "type": "Protein", "text": [ "granulocyte-macrophage-colony stimulating factor" ], "offsets": [ [ 942, 990 ] ], "normalized": [] }, { "id": "PMID-14550269_T8", "type": "Protein", "text": [ "GM-CSF" ], "offsets": [ [ 992, 998 ] ], "normalized": [] }, { "id": "PMID-14550269_T9", "type": "Protein", "text": [ "tumor necrosis factor" ], "offsets": [ [ 1001, 1022 ] ], "normalized": [] }, { "id": "PMID-14550269_T10", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1024, 1033 ] ], "normalized": [] }, { "id": "PMID-14550269_T11", "type": "Protein", "text": [ "interleukin (IL)-4" ], "offsets": [ [ 1066, 1084 ] ], "normalized": [] }, { "id": "PMID-14550269_T12", "type": "Protein", "text": [ "CLECSF6" ], "offsets": [ [ 1125, 1132 ] ], "normalized": [] } ]

[ { "id": "PMID-14550269_E1", "type": "Deglycosylation", "trigger": { "text": [ "deglycosylated" ], "offsets": [ [ 685, 699 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14550269_T6" } ] } ]

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[]

[ { "id": "PMID-14551338__text", "type": "abstract", "text": [ "Epigenetic switch from posttranscriptional to transcriptional silencing is correlated with promoter hypermethylation. \nChanges in the distribution of methylcytosine residues along a transgene locus of tobacco (Nicotiana tabacum) in relation to the type of gene silencing were studied in parental plant leaves, calli, and regenerated plants derived thereof. Parental-silenced HeLo1 (hemizygous for locus 1) plants show posttranscriptional silencing of the residing nptII (neomycin phosphotransferase II) transgene and cytosine methylation restricted to the 3' end and center part of the transcribed region. Here, we report that with an increasing number of cell cycles, DNA methylation changes gradually, and methylation is introduced into the promoter during cell culture and more slowly in vegetatively propagated plants. After 24 months of callus in vitro cultivation, an epigenetic variant, designated locus 1E, was obtained in which cytosine methylation of symmetrical (CG and CNG) sites was almost complete within the 5' end of the nptII-transcribed region and the 35S promoter. Further, methylation of nonsymmetrical sites appeared de novo in the promoter, whereas this type of methylation was significantly reduced in the 3' end of the transcribed region when compared with locus 1. The newly established epigenetic patterns were stably transmitted from calli into regenerated plants and their progeny. The protein and steady-state RNA levels remained low in locus 1E, whereas with nuclear run-on assays, no detectable amounts of primary transcripts were found along the nptII gene, indicating that the methylated promoter became inactivated. The results suggest that a switch between posttranscriptional and transcriptional gene silencing could be a mechanism leading to irrevocable shut down of gene expression within a finite number of generations.\n" ], "offsets": [ [ 0, 1859 ] ] } ]

[ { "id": "PMID-14551338_T1", "type": "Protein", "text": [ "nptII" ], "offsets": [ [ 464, 469 ] ], "normalized": [] }, { "id": "PMID-14551338_T2", "type": "Protein", "text": [ "neomycin phosphotransferase II" ], "offsets": [ [ 471, 501 ] ], "normalized": [] }, { "id": "PMID-14551338_T3", "type": "Protein", "text": [ "nptII" ], "offsets": [ [ 1037, 1042 ] ], "normalized": [] }, { "id": "PMID-14551338_T4", "type": "Protein", "text": [ "nptII" ], "offsets": [ [ 1578, 1583 ] ], "normalized": [] }, { "id": "PMID-14551338_T6", "type": "Entity", "text": [ "3' end" ], "offsets": [ [ 556, 562 ] ], "normalized": [] }, { "id": "PMID-14551338_T7", "type": "Entity", "text": [ "center part" ], "offsets": [ [ 567, 578 ] ], "normalized": [] }, { "id": "PMID-14551338_T9", "type": "Entity", "text": [ "5' end" ], "offsets": [ [ 1023, 1029 ] ], "normalized": [] }, { "id": "PMID-14551338_T10", "type": "Entity", "text": [ "35S promoter" ], "offsets": [ [ 1070, 1082 ] ], "normalized": [] }, { "id": "PMID-14551338_T12", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1153, 1161 ] ], "normalized": [] }, { "id": "PMID-14551338_T13", "type": "Entity", "text": [ "transcribed region" ], "offsets": [ [ 1243, 1261 ] ], "normalized": [] }, { "id": "PMID-14551338_T15", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1621, 1629 ] ], "normalized": [] } ]

[ { "id": "PMID-14551338_E1", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 526, 537 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14551338_T1" }, { "role": "Site", "ref_id": "PMID-14551338_T6" } ] }, { "id": "PMID-14551338_E2", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 526, 537 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14551338_T1" }, { "role": "Site", "ref_id": "PMID-14551338_T7" } ] }, { "id": "PMID-14551338_E3", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 946, 957 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14551338_T3" }, { "role": "Site", "ref_id": "PMID-14551338_T9" } ] }, { "id": "PMID-14551338_E4", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 946, 957 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14551338_T3" }, { "role": "Site", "ref_id": "PMID-14551338_T10" } ] }, { "id": "PMID-14551338_E5", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1093, 1104 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14551338_T3" }, { "role": "Site", "ref_id": "PMID-14551338_T12" } ] }, { "id": "PMID-14551338_E6", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1093, 1104 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14551338_T3" }, { "role": "Site", "ref_id": "PMID-14551338_T13" } ] }, { "id": "PMID-14551338_E7", "type": "DNA_methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 1610, 1620 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14551338_T4" }, { "role": "Site", "ref_id": "PMID-14551338_T15" } ] } ]

[ { "id": "PMID-14551338_1", "entity_ids": [ "PMID-14551338_T1", "PMID-14551338_T2" ] } ]

[]

[ { "id": "PMID-14556920__text", "type": "abstract", "text": [ "Frequent methylation of p16INK4A and p14ARF genes implicated in the evolution of chronic myeloid leukaemia from its chronic to accelerated phase. \nThe frequency and mechanism of p16(INK4A) and p14(ARF) gene alterations were studied in cell samples from 30 patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukaemia (CML), both at diagnosis and at the onset of the accelerated phase (AP) of the disease. No alterations in the p16(INK4A) or p14(ARF) genes were found in any of the chronic phase (CP) samples. DNA sequencing analyses detected p16(INK4A) or p14(ARF) mutations in 17 AP samples. All mutations were heterozygous without loss of the other allele. Aberrant methylation of the p16(INK4A) or p14(ARF) promoters was found in 14 of 30 AP samples. The most common situation was the simultaneous methylation of both promoters. Our data indicate that p16(INK4A) and p14(ARF) are primary targets for inactivation by promoter methylation in the acceleration of CML. Transcriptional silencing of the p16(INK4A) and p14(ARF) genes may be important in the conversion of CML from the CP to the AP.\n" ], "offsets": [ [ 0, 1113 ] ] } ]

[ { "id": "PMID-14556920_T1", "type": "Protein", "text": [ "p16INK4A" ], "offsets": [ [ 24, 32 ] ], "normalized": [] }, { "id": "PMID-14556920_T2", "type": "Protein", "text": [ "p14ARF" ], "offsets": [ [ 37, 43 ] ], "normalized": [] }, { "id": "PMID-14556920_T3", "type": "Protein", "text": [ "p16(INK4A)" ], "offsets": [ [ 178, 188 ] ], "normalized": [] }, { "id": "PMID-14556920_T4", "type": "Protein", "text": [ "p14(ARF)" ], "offsets": [ [ 193, 201 ] ], "normalized": [] }, { "id": "PMID-14556920_T5", "type": "Protein", "text": [ "p16(INK4A)" ], "offsets": [ [ 444, 454 ] ], "normalized": [] }, { "id": "PMID-14556920_T6", "type": "Protein", "text": [ "p14(ARF)" ], "offsets": [ [ 458, 466 ] ], "normalized": [] }, { "id": "PMID-14556920_T7", "type": "Protein", "text": [ "p16(INK4A)" ], "offsets": [ [ 559, 569 ] ], "normalized": [] }, { "id": "PMID-14556920_T8", "type": "Protein", "text": [ "p14(ARF)" ], "offsets": [ [ 573, 581 ] ], "normalized": [] }, { "id": "PMID-14556920_T9", "type": "Protein", "text": [ "p16(INK4A)" ], "offsets": [ [ 704, 714 ] ], "normalized": [] }, { "id": "PMID-14556920_T10", "type": "Protein", "text": [ "p14(ARF)" ], "offsets": [ [ 718, 726 ] ], "normalized": [] }, { "id": "PMID-14556920_T11", "type": "Protein", "text": [ "p16(INK4A)" ], "offsets": [ [ 872, 882 ] ], "normalized": [] }, { "id": "PMID-14556920_T12", "type": "Protein", "text": [ "p14(ARF)" ], "offsets": [ [ 887, 895 ] ], "normalized": [] }, { "id": "PMID-14556920_T13", "type": "Protein", "text": [ "p16(INK4A)" ], "offsets": [ [ 1018, 1028 ] ], "normalized": [] }, { "id": "PMID-14556920_T14", "type": "Protein", "text": [ "p14(ARF)" ], "offsets": [ [ 1033, 1041 ] ], "normalized": [] }, { "id": "PMID-14556920_T17", "type": "Entity", "text": [ "promoters" ], "offsets": [ [ 727, 736 ] ], "normalized": [] }, { "id": "PMID-14556920_T19", "type": "Entity", "text": [ "promoters" ], "offsets": [ [ 838, 847 ] ], "normalized": [] }, { "id": "PMID-14556920_T20", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 936, 944 ] ], "normalized": [] } ]

[ { "id": "PMID-14556920_E1", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 9, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14556920_T1" } ] }, { "id": "PMID-14556920_E2", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 9, 20 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14556920_T2" } ] }, { "id": "PMID-14556920_E3", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 685, 696 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14556920_T9" }, { "role": "Site", "ref_id": "PMID-14556920_T17" } ] }, { "id": "PMID-14556920_E4", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 685, 696 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14556920_T10" }, { "role": "Site", "ref_id": "PMID-14556920_T17" } ] }, { "id": "PMID-14556920_E5", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 818, 829 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14556920_T9" }, { "role": "Site", "ref_id": "PMID-14556920_T19" } ] }, { "id": "PMID-14556920_E6", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 818, 829 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14556920_T10" }, { "role": "Site", "ref_id": "PMID-14556920_T19" } ] }, { "id": "PMID-14556920_E7", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 945, 956 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14556920_T11" }, { "role": "Site", "ref_id": "PMID-14556920_T20" } ] }, { "id": "PMID-14556920_E8", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 945, 956 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14556920_T12" }, { "role": "Site", "ref_id": "PMID-14556920_T20" } ] } ]

[]

[]

[ { "id": "PMID-14559996__text", "type": "abstract", "text": [ "mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the Myc target gene cad. \nThe role of hSWI/SNF complexes in transcriptional activation is well characterized; however, little is known about their function in transcriptional repression. We have previously shown that subunits of the mSin3A/histone deacetylase 2 (HDAC2) corepressor complex copurify with hSWI/SNF complexes. Here we show that the type II arginine-specific methyltransferase PRMT5, which is involved in cyclin E repression, can be found in association with Brg1 and hBrm-based hSWI/SNF complexes. We also show that hSWI/SNF-associated PRMT5 can methylate hypoacetylated histones H3 and H4 more efficiently than hyperacetylated histones H3 and H4. Protein-protein interaction studies indicate that PRMT5 and mSin3A interact with the same hSWI/SNF subunits as those targeted by c-Myc. These observations prompted us to examine the expression profile of the c-Myc target genes, carbamoyl-phosphate synthase-aspartate carbamoyltransferase-dihydroorotase (cad) and nucleolin (nuc). We found that cad repression is altered in cells that express inactive Brg1 and in cells treated with the HDAC inhibitor depsipeptide. Using chromatin immunoprecipitation assays, we found that Brg1, mSin3A, HDAC2, and PRMT5 are directly recruited to the cad promoter. These results suggest that hSWI/SNF complexes, through their ability to interact with activator and repressor proteins, control expression of genes involved in cell growth and proliferation.\n" ], "offsets": [ [ 0, 1560 ] ] } ]

[ { "id": "PMID-14559996_T1", "type": "Protein", "text": [ "Sin3A" ], "offsets": [ [ 1, 6 ] ], "normalized": [] }, { "id": "PMID-14559996_T2", "type": "Protein", "text": [ "histone deacetylase 2" ], "offsets": [ [ 7, 28 ] ], "normalized": [] }, { "id": "PMID-14559996_T3", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 34, 39 ] ], "normalized": [] }, { "id": "PMID-14559996_T4", "type": "Protein", "text": [ "Brg1" ], "offsets": [ [ 51, 55 ] ], "normalized": [] }, { "id": "PMID-14559996_T5", "type": "Protein", "text": [ "Myc" ], "offsets": [ [ 113, 116 ] ], "normalized": [] }, { "id": "PMID-14559996_T6", "type": "Protein", "text": [ "cad" ], "offsets": [ [ 129, 132 ] ], "normalized": [] }, { "id": "PMID-14559996_T7", "type": "Protein", "text": [ "Sin3A" ], "offsets": [ [ 343, 348 ] ], "normalized": [] }, { "id": "PMID-14559996_T8", "type": "Protein", "text": [ "histone deacetylase 2" ], "offsets": [ [ 349, 370 ] ], "normalized": [] }, { "id": "PMID-14559996_T9", "type": "Protein", "text": [ "HDAC2" ], "offsets": [ [ 372, 377 ] ], "normalized": [] }, { "id": "PMID-14559996_T10", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 499, 504 ] ], "normalized": [] }, { "id": "PMID-14559996_T11", "type": "Protein", "text": [ "Brg1" ], "offsets": [ [ 581, 585 ] ], "normalized": [] }, { "id": "PMID-14559996_T12", "type": "Protein", "text": [ "Brm" ], "offsets": [ [ 591, 594 ] ], "normalized": [] }, { "id": "PMID-14559996_T13", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 659, 664 ] ], "normalized": [] }, { "id": "PMID-14559996_T14", "type": "Protein", "text": [ "histones H3" ], "offsets": [ [ 694, 705 ] ], "normalized": [] }, { "id": "PMID-14559996_T15", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 710, 712 ] ], "normalized": [] }, { "id": "PMID-14559996_T16", "type": "Protein", "text": [ "histones H3" ], "offsets": [ [ 751, 762 ] ], "normalized": [] }, { "id": "PMID-14559996_T17", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 767, 769 ] ], "normalized": [] }, { "id": "PMID-14559996_T18", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 821, 826 ] ], "normalized": [] }, { "id": "PMID-14559996_T19", "type": "Protein", "text": [ "Sin3A" ], "offsets": [ [ 832, 837 ] ], "normalized": [] }, { "id": "PMID-14559996_T20", "type": "Protein", "text": [ "c-Myc" ], "offsets": [ [ 900, 905 ] ], "normalized": [] }, { "id": "PMID-14559996_T21", "type": "Protein", "text": [ "c-Myc" ], "offsets": [ [ 979, 984 ] ], "normalized": [] }, { "id": "PMID-14559996_T22", "type": "Protein", "text": [ "carbamoyl-phosphate synthase" ], "offsets": [ [ 999, 1027 ] ], "normalized": [] }, { "id": "PMID-14559996_T23", "type": "Protein", "text": [ "aspartate carbamoyltransferase" ], "offsets": [ [ 1028, 1058 ] ], "normalized": [] }, { "id": "PMID-14559996_T24", "type": "Protein", "text": [ "dihydroorotase" ], "offsets": [ [ 1059, 1073 ] ], "normalized": [] }, { "id": "PMID-14559996_T25", "type": "Protein", "text": [ "cad" ], "offsets": [ [ 1075, 1078 ] ], "normalized": [] }, { "id": "PMID-14559996_T26", "type": "Protein", "text": [ "nucleolin" ], "offsets": [ [ 1084, 1093 ] ], "normalized": [] }, { "id": "PMID-14559996_T27", "type": "Protein", "text": [ "nuc" ], "offsets": [ [ 1095, 1098 ] ], "normalized": [] }, { "id": "PMID-14559996_T28", "type": "Protein", "text": [ "cad" ], "offsets": [ [ 1115, 1118 ] ], "normalized": [] }, { "id": "PMID-14559996_T29", "type": "Protein", "text": [ "Brg1" ], "offsets": [ [ 1172, 1176 ] ], "normalized": [] }, { "id": "PMID-14559996_T30", "type": "Protein", "text": [ "Brg1" ], "offsets": [ [ 1294, 1298 ] ], "normalized": [] }, { "id": "PMID-14559996_T31", "type": "Protein", "text": [ "Sin3A" ], "offsets": [ [ 1301, 1306 ] ], "normalized": [] }, { "id": "PMID-14559996_T32", "type": "Protein", "text": [ "HDAC2" ], "offsets": [ [ 1308, 1313 ] ], "normalized": [] }, { "id": "PMID-14559996_T33", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 1319, 1324 ] ], "normalized": [] }, { "id": "PMID-14559996_T34", "type": "Protein", "text": [ "cad" ], "offsets": [ [ 1355, 1358 ] ], "normalized": [] } ]

[ { "id": "PMID-14559996_E1", "type": "Catalysis", "trigger": { "text": [ "methylate" ], "offsets": [ [ 669, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14559996_E8" }, { "role": "Cause", "ref_id": "PMID-14559996_T13" } ] }, { "id": "PMID-14559996_E2", "type": "Methylation", "trigger": { "text": [ "methylate" ], "offsets": [ [ 669, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14559996_T17" } ] }, { "id": "PMID-14559996_E3", "type": "Catalysis", "trigger": { "text": [ "methylate" ], "offsets": [ [ 669, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14559996_E2" }, { "role": "Cause", "ref_id": "PMID-14559996_T13" } ] }, { "id": "PMID-14559996_E4", "type": "Methylation", "trigger": { "text": [ "methylate" ], "offsets": [ [ 669, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14559996_T14" } ] }, { "id": "PMID-14559996_E5", "type": "Catalysis", "trigger": { "text": [ "methylate" ], "offsets": [ [ 669, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14559996_E4" }, { "role": "Cause", "ref_id": "PMID-14559996_T13" } ] }, { "id": "PMID-14559996_E6", "type": "Methylation", "trigger": { "text": [ "methylate" ], "offsets": [ [ 669, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14559996_T15" } ] }, { "id": "PMID-14559996_E7", "type": "Catalysis", "trigger": { "text": [ "methylate" ], "offsets": [ [ 669, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14559996_E6" }, { "role": "Cause", "ref_id": "PMID-14559996_T13" } ] }, { "id": "PMID-14559996_E8", "type": "Methylation", "trigger": { "text": [ "methylate" ], "offsets": [ [ 669, 678 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14559996_T16" } ] }, { "id": "PMID-14559996_E9", "type": "Deacetylation", "trigger": { "text": [ "hypoacetylated" ], "offsets": [ [ 679, 693 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14559996_T14" } ] }, { "id": "PMID-14559996_E10", "type": "Deacetylation", "trigger": { "text": [ "hypoacetylated" ], "offsets": [ [ 679, 693 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14559996_T15" } ] }, { "id": "PMID-14559996_E11", "type": "Acetylation", "trigger": { "text": [ "hyperacetylated" ], "offsets": [ [ 735, 750 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14559996_T16" } ] }, { "id": "PMID-14559996_E12", "type": "Acetylation", "trigger": { "text": [ "hyperacetylated" ], "offsets": [ [ 735, 750 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14559996_T17" } ] } ]

[ { "id": "PMID-14559996_1", "entity_ids": [ "PMID-14559996_T8", "PMID-14559996_T9" ] }, { "id": "PMID-14559996_2", "entity_ids": [ "PMID-14559996_T22", "PMID-14559996_T23", "PMID-14559996_T24", "PMID-14559996_T25" ] }, { "id": "PMID-14559996_3", "entity_ids": [ "PMID-14559996_T26", "PMID-14559996_T27" ] } ]

[]

[ { "id": "PMID-14561399__text", "type": "abstract", "text": [ "Centromere silencing and function in fission yeast is governed by the amino terminus of histone H3. \nBACKGROUND: Centromeric domains often consist of repetitive elements that are assembled in specialized chromatin, characterized by hypoacetylation of histones H3 and H4 and methylation of lysine 9 of histone H3 (K9-MeH3). Perturbation of this underacetylated state by transient treatment with histone deacetylase inhibitors leads to defective centromere function, correlating with delocalization of the heterochromatin protein Swi6/HP1. Likewise, deletion of the K9-MeH3 methyltransferase Clr4/Suvar39 causes defective chromosome segregation. Here, we create fission yeast strains retaining one histone H3 and H4 gene; the creation of these strains allows mutation of specific N-terminal tail residues and their role in centromeric silencing and chromosome stability to be investigated. RESULTS: Reduction of H3/H4 gene dosage to one-third does not affect cell viability or heterochromatin formation. Mutation of lysines 9 or 14 or serine 10 within the amino terminus of histone H3 impairs centromere function, leading to defective chromosome segregation and Swi6 delocalization. Surprisingly, silent centromeric chromatin does not require the conserved lysine 8 and 16 residues of histone H4. CONCLUSIONS: To date, mutation of conserved N-terminal residues in endogenous histone genes has only been performed in budding yeast, which lacks the Clr4/Suvar39 histone methyltransferase and Swi6/HP1. We demonstrate the importance of conserved residues within the histone H3 N terminus for the maintenance of centromeric heterochromatin in fission yeast. In sharp contrast, mutation of two conserved lysines within the histone H4 tail has no impact on the integrity of centromeric heterochromatin. Our data highlight the striking divergence between the histone tail requirements for the fission yeast and budding yeast silencing pathways.\n" ], "offsets": [ [ 0, 1936 ] ] } ]

[ { "id": "PMID-14561399_T1", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 88, 98 ] ], "normalized": [] }, { "id": "PMID-14561399_T2", "type": "Protein", "text": [ "histones H3" ], "offsets": [ [ 251, 262 ] ], "normalized": [] }, { "id": "PMID-14561399_T3", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 267, 269 ] ], "normalized": [] }, { "id": "PMID-14561399_T4", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 301, 311 ] ], "normalized": [] }, { "id": "PMID-14561399_T5", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 318, 320 ] ], "normalized": [] }, { "id": "PMID-14561399_T6", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 394, 401 ] ], "normalized": [] }, { "id": "PMID-14561399_T7", "type": "Protein", "text": [ "Swi6" ], "offsets": [ [ 528, 532 ] ], "normalized": [] }, { "id": "PMID-14561399_T8", "type": "Protein", "text": [ "HP1" ], "offsets": [ [ 533, 536 ] ], "normalized": [] }, { "id": "PMID-14561399_T9", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 569, 571 ] ], "normalized": [] }, { "id": "PMID-14561399_T10", "type": "Protein", "text": [ "Clr4" ], "offsets": [ [ 590, 594 ] ], "normalized": [] }, { "id": "PMID-14561399_T11", "type": "Protein", "text": [ "Suvar39" ], "offsets": [ [ 595, 602 ] ], "normalized": [] }, { "id": "PMID-14561399_T12", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 696, 706 ] ], "normalized": [] }, { "id": "PMID-14561399_T13", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 711, 713 ] ], "normalized": [] }, { "id": "PMID-14561399_T14", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 910, 912 ] ], "normalized": [] }, { "id": "PMID-14561399_T15", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 913, 915 ] ], "normalized": [] }, { "id": "PMID-14561399_T16", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 1072, 1082 ] ], "normalized": [] }, { "id": "PMID-14561399_T17", "type": "Protein", "text": [ "Swi6" ], "offsets": [ [ 1160, 1164 ] ], "normalized": [] }, { "id": "PMID-14561399_T18", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 1283, 1293 ] ], "normalized": [] }, { "id": "PMID-14561399_T19", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1373, 1380 ] ], "normalized": [] }, { "id": "PMID-14561399_T20", "type": "Protein", "text": [ "Clr4" ], "offsets": [ [ 1445, 1449 ] ], "normalized": [] }, { "id": "PMID-14561399_T21", "type": "Protein", "text": [ "Suvar39" ], "offsets": [ [ 1450, 1457 ] ], "normalized": [] }, { "id": "PMID-14561399_T22", "type": "Protein", "text": [ "Swi6" ], "offsets": [ [ 1488, 1492 ] ], "normalized": [] }, { "id": "PMID-14561399_T23", "type": "Protein", "text": [ "HP1" ], "offsets": [ [ 1493, 1496 ] ], "normalized": [] }, { "id": "PMID-14561399_T24", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 1561, 1571 ] ], "normalized": [] }, { "id": "PMID-14561399_T25", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 1716, 1726 ] ], "normalized": [] }, { "id": "PMID-14561399_T26", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1850, 1857 ] ], "normalized": [] }, { "id": "PMID-14561399_T29", "type": "Entity", "text": [ "lysine 9" ], "offsets": [ [ 289, 297 ] ], "normalized": [] }, { "id": "PMID-14561399_T30", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 313, 315 ] ], "normalized": [] } ]

[ { "id": "PMID-14561399_E1", "type": "Acetylation", "trigger": { "text": [ "hypoacetylation" ], "offsets": [ [ 232, 247 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14561399_T2" } ] }, { "id": "PMID-14561399_E2", "type": "Acetylation", "trigger": { "text": [ "hypoacetylation" ], "offsets": [ [ 232, 247 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14561399_T3" } ] }, { "id": "PMID-14561399_E3", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 274, 285 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14561399_T4" }, { "role": "Site", "ref_id": "PMID-14561399_T29" } ] } ]

[ { "id": "PMID-14561399_1", "entity_ids": [ "PMID-14561399_T29", "PMID-14561399_T30" ] }, { "id": "PMID-14561399_2", "entity_ids": [ "PMID-14561399_T4", "PMID-14561399_T5" ] } ]

[]

[ { "id": "PMID-14660666__text", "type": "abstract", "text": [ "Thermal stability and aggregation of sulfolobus solfataricus beta-glycosidase are dependent upon the N-epsilon-methylation of specific lysyl residues: critical role of in vivo post-translational modifications. \nMethylation in vivo is a post-translational modification observed in several organisms belonging to eucarya, bacteria, and archaea. Although important implications of this modification have been demonstrated in several eucaryotes, its biological role in hyperthermophilic archaea is far from being understood. The aim of this work is to clarify some effects of methylation on the properties of beta-glycosidase from Sulfolobus solfataricus, by a structural comparison between the native, methylated protein and its unmethylated counterpart, recombinantly expressed in Escherichia coli. Analysis by Fourier transform infrared spectroscopy indicated similar secondary structure contents for the two forms of the protein. However, the study of temperature perturbation by Fourier transform infrared spectroscopy and turbidimetry evidenced denaturation and aggregation events more pronounced in recombinant than in native beta-glycosidase. Red Nile fluorescence analysis revealed significant differences of surface hydrophobicity between the two forms of the protein. Unlike the native enzyme, which dissociated into SDS-resistant dimers upon exposure to the detergent, the recombinant enzyme partially dissociated into monomers. By electrospray mapping, the methylation sites of the native protein were identified. A computational analysis of beta-glycosidase three-dimensional structure and comparisons with other proteins from S. solfataricus revealed analogies in the localization of methylation sites in terms of secondary structural elements and overall topology. These observations suggest a role for the methylation of lysyl residues, located in selected domains, in the thermal stabilization of beta-glycosidase from S. solfataricus.\n" ], "offsets": [ [ 0, 1950 ] ] } ]

[ { "id": "PMID-14660666_T1", "type": "Protein", "text": [ "beta-glycosidase" ], "offsets": [ [ 61, 77 ] ], "normalized": [] }, { "id": "PMID-14660666_T2", "type": "Protein", "text": [ "beta-glycosidase" ], "offsets": [ [ 605, 621 ] ], "normalized": [] }, { "id": "PMID-14660666_T3", "type": "Protein", "text": [ "beta-glycosidase" ], "offsets": [ [ 1129, 1145 ] ], "normalized": [] }, { "id": "PMID-14660666_T4", "type": "Protein", "text": [ "beta-glycosidase" ], "offsets": [ [ 1551, 1567 ] ], "normalized": [] }, { "id": "PMID-14660666_T5", "type": "Protein", "text": [ "beta-glycosidase" ], "offsets": [ [ 1911, 1927 ] ], "normalized": [] }, { "id": "PMID-14660666_T7", "type": "Entity", "text": [ "lysyl residues" ], "offsets": [ [ 135, 149 ] ], "normalized": [] }, { "id": "PMID-14660666_T11", "type": "Entity", "text": [ "lysyl residues" ], "offsets": [ [ 1834, 1848 ] ], "normalized": [] } ]

[ { "id": "PMID-14660666_E1", "type": "Methylation", "trigger": { "text": [ "N-epsilon-methylation" ], "offsets": [ [ 101, 122 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14660666_T1" }, { "role": "Site", "ref_id": "PMID-14660666_T7" } ] }, { "id": "PMID-14660666_E2", "type": "Methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 699, 709 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14660666_T2" } ] }, { "id": "PMID-14660666_E3", "type": "Methylation", "trigger": { "text": [ "unmethylated" ], "offsets": [ [ 726, 738 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14660666_T2" } ] }, { "id": "PMID-14660666_E4", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1819, 1830 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-14660666_T5" }, { "role": "Site", "ref_id": "PMID-14660666_T11" } ] } ]

[]

[]

[ { "id": "PMID-14663079__text", "type": "abstract", "text": [ "Pathways for phosphatidylcholine biosynthesis in bacteria. \nPhosphatidylcholine (PC) is the major membrane-forming phospholipid in eukaryotes with important structural and signalling functions. Although many prokaryotes lack PC, it can be found in significant amounts in membranes of rather diverse bacteria. Two pathways for PC biosynthesis are known in bacteria, the methylation pathway and the phosphatidylcholine synthase (PCS) pathway. In the methylation pathway, phosphatidylethanolamine is methylated three times to yield PC, in reactions catalysed by one or several phospholipid N-methyltransferases (PMTs). In the PCS pathway, choline is condensed directly with CDP-diacylglyceride to form PC in a reaction catalysed by PCS. Using cell-free extracts, it was demonstrated that Sinorhizobium meliloti, Agrobacterium tumefaciens, Rhizobium leguminosarum, Bradyrhizobium japonicum, Mesorhizobium loti and Legionella pneumophila have both PMT and PCS activities. In addition, Rhodobacter sphaeroides has PMT activity and Brucella melitensis, Pseudomonas aeruginosa and Borrelia burgdorferi have PCS activities. Genes from M. loti and L. pneumophila encoding a Pmt or a Pcs activity and the genes from P. aeruginosa and Borrelia burgdorferi responsible for Pcs activity have been identified. Based on these functional assignments and on genomic data, one might predict that if bacteria contain PC as a membrane lipid, they usually possess both bacterial pathways for PC biosynthesis. However, important pathogens such as Brucella melitensis, P. aeruginosa and Borrelia burgdorferi seem to be exceptional as they possess only the PCS pathway for PC formation.\n" ], "offsets": [ [ 0, 1662 ] ] } ]

[ { "id": "PMID-14663079_T1", "type": "Protein", "text": [ "phosphatidylcholine synthase" ], "offsets": [ [ 397, 425 ] ], "normalized": [] }, { "id": "PMID-14663079_T2", "type": "Protein", "text": [ "PCS" ], "offsets": [ [ 427, 430 ] ], "normalized": [] }, { "id": "PMID-14663079_T3", "type": "Protein", "text": [ "PCS" ], "offsets": [ [ 951, 954 ] ], "normalized": [] }, { "id": "PMID-14663079_T4", "type": "Protein", "text": [ "Pmt" ], "offsets": [ [ 1164, 1167 ] ], "normalized": [] }, { "id": "PMID-14663079_T5", "type": "Protein", "text": [ "Pcs" ], "offsets": [ [ 1173, 1176 ] ], "normalized": [] }, { "id": "PMID-14663079_T6", "type": "Protein", "text": [ "Pcs" ], "offsets": [ [ 1260, 1263 ] ], "normalized": [] }, { "id": "PMID-14663079_T7", "type": "Protein", "text": [ "PCS" ], "offsets": [ [ 1632, 1635 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-14663079_1", "entity_ids": [ "PMID-14663079_T1", "PMID-14663079_T2" ] } ]

[]

[ { "id": "PMID-14755618__text", "type": "abstract", "text": [ "Rapid screening for S-adenosylmethionine-dependent methylation products by enzyme-transferred isotope patterns analysis. \nWe report here an isotopic labeling and mass spectrometric method to rapidly identify S-adenosylmethionine (AdoMet)-dependent methylation products. In the presence of CH(3)- and CD(3)-labeled AdoMet, a methyl transfer product appears as a doublet separated by 3 Da in a mass spectrum, while other compounds show their normal isotopic distribution. Based on this unique isotopic pattern, methylation product(s) can be easily detected even from a mixture of cellular components. To validate our method, the product of human thiopurine methyltransferase (TPMT, EC 2.1.1.67) has been successfully identified from both an in vitro assay and a whole-cell assay. This method is generally applicable to AdoMet-dependent transmethylation and other group-transfer reactions, and constitutes the first example of a general strategy of enzyme-transferred isotope patterns (ETIPs) analysis.\n" ], "offsets": [ [ 0, 1000 ] ] } ]

[ { "id": "PMID-14755618_T1", "type": "Protein", "text": [ "thiopurine methyltransferase" ], "offsets": [ [ 644, 672 ] ], "normalized": [] }, { "id": "PMID-14755618_T2", "type": "Protein", "text": [ "TPMT" ], "offsets": [ [ 674, 678 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-14755618_1", "entity_ids": [ "PMID-14755618_T1", "PMID-14755618_T2" ] } ]

[]

[ { "id": "PMID-1498420__text", "type": "abstract", "text": [ "Subunit-specific sulphation of oligosaccharides relating to charge-heterogeneity in porcine lutrophin isoforms. \nLutrophin (LH) consists of an array of isoforms with different charges and bioactivities. This study was undertaken to clarify specifically how oligosaccharides of alpha and beta subunits contribute to LH isoform charges. Porcine LH (pLH) was separated into four isoforms by isoelectric focusing (IEF), followed by subunit isolation. Their oligosaccharides were released by hydrazinolysis, labelled by reduction with NaB3H4, and fractionated by HPLC with a Mono Q column into five populations differing in the number of sulphate (S) and sialic acid (N) residues, designated as Neutral, N-1, S-1, S-N and S-2. Oligosaccharides were predominantly sulphated (S-1 and S-2) and infrequently sialylated (N-1 and S-N). Further analysis, including concanavalin A (Con A) affinity chromatography, desialylation, desulphation, sequential exoglycosidase digestion and methylation, clarified the structures of the acidic oligosaccharides. All were of the biantennary complex type. Their two peripheral branches were SO4-4GalNAc beta 1-4Glc-NAc and GalNAc beta 1-4GlcNAc or GlcNAc in S-1, SO4-4GalNAc beta 1-4GlcNAc and Sia alpha 2-6Gal beta 1-4GlcNAc in S-N, and (SO4-4GalNAc beta 1-4GlcNAc)2 in S-2 (where GalNAc is N-acetylgalactosamine and GlcNAc is N-acetylglucosamine). Ten percent of S-1 and of S-N had a bisecting GlcNAc residue. Sulphate residues occurred in nearly the same amount for both subunits; however, the alpha and beta subunits were sulphated differently. S-1 predominated in the alpha subunit, while S-1 and S-2 were major components in the beta subunit.(ABSTRACT TRUNCATED AT 250 WORDS)\n" ], "offsets": [ [ 0, 1708 ] ] } ]

[ { "id": "PMID-1498420_T1", "type": "Protein", "text": [ "concanavalin A" ], "offsets": [ [ 853, 867 ] ], "normalized": [] }, { "id": "PMID-1498420_T2", "type": "Protein", "text": [ "Con A" ], "offsets": [ [ 869, 874 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-1498420_1", "entity_ids": [ "PMID-1498420_T1", "PMID-1498420_T2" ] } ]

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[ { "id": "PMID-15033905__text", "type": "abstract", "text": [ "The MTHFR 677C > T polymorphism is associated with an increased risk of hepatocellular carcinoma in patients with alcoholic cirrhosis. \nMethylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, plays a major role in the provision of methyl groups for DNA methylation and in the production of dTMP for DNA synthesis. Different polymorphisms have been described for this enzyme, the most studied being the C677T, which has been shown to be associated with predisposition to colorectal cancer in patients who consume a high alcohol diet. The aim of this study was to determine whether the MTHFR polymorphism is related to hepatocellular carcinoma (HCC) in patients with alcoholic cirrhosis. MTHFR genotypes were determined in 300 liver transplant patients, 72 of whom had alcoholic cirrhosis with HCC and 122 of whom had alcoholic cirrhosis without HCC. The remaining patients were transplanted for HCC on normal liver (n = 27) or viral cirrhosis with HCC (n = 49) or without HCC (n = 30). We also tested 80 healthy subjects. Among the group of patients transplanted for alcoholic cirrhosis, the frequency of MTHFR variants CC versus CT and TT was significantly higher in patients with HCC than in patients without macroscopic evidence of HCC (P = 0.02). This difference was not observed between patients with and without HCC developed either on viral cirrhosis or on non-cirrhotic liver. If we considered all the patients transplanted for HCC, the MTHFR CC genotype was significantly higher in patients who had developed HCC on alcoholic cirrhosis rather than on viral cirrhosis (P = 0.002) or on non-cirrhotic livers (P = 0.02). The relative risk for HCC in subjects with alcoholic cirrhosis and the CC genotype was 2.03. These results suggest that the MTHFR CC genotype increases the risk to develop HCC in patients who consume a high alcohol diet.\n" ], "offsets": [ [ 0, 1871 ] ] } ]

[ { "id": "PMID-15033905_T1", "type": "Protein", "text": [ "MTHFR" ], "offsets": [ [ 4, 9 ] ], "normalized": [] }, { "id": "PMID-15033905_T2", "type": "Protein", "text": [ "Methylenetetrahydrofolate reductase" ], "offsets": [ [ 136, 171 ] ], "normalized": [] }, { "id": "PMID-15033905_T3", "type": "Protein", "text": [ "MTHFR" ], "offsets": [ [ 173, 178 ] ], "normalized": [] }, { "id": "PMID-15033905_T4", "type": "Protein", "text": [ "MTHFR" ], "offsets": [ [ 608, 613 ] ], "normalized": [] }, { "id": "PMID-15033905_T5", "type": "Protein", "text": [ "MTHFR" ], "offsets": [ [ 710, 715 ] ], "normalized": [] }, { "id": "PMID-15033905_T6", "type": "Protein", "text": [ "MTHFR" ], "offsets": [ [ 1128, 1133 ] ], "normalized": [] }, { "id": "PMID-15033905_T7", "type": "Protein", "text": [ "MTHFR" ], "offsets": [ [ 1468, 1473 ] ], "normalized": [] }, { "id": "PMID-15033905_T8", "type": "Protein", "text": [ "MTHFR" ], "offsets": [ [ 1774, 1779 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-15033905_1", "entity_ids": [ "PMID-15033905_T2", "PMID-15033905_T3" ] } ]

[]

[ { "id": "PMID-15060159__text", "type": "abstract", "text": [ "Mbd1 is recruited to both methylated and nonmethylated CpGs via distinct DNA binding domains. \nMBD1 is a vertebrate methyl-CpG binding domain protein (MBD) that can bring about repression of methylated promoter DNA sequences. Like other MBD proteins, MBD1 localizes to nuclear foci that in mice are rich in methyl-CpG. In methyl-CpG-deficient mouse cells, however, Mbd1 remains localized to heterochromatic foci whereas other MBD proteins become dispersed in the nucleus. We find that Mbd1a, a major mouse isoform, contains a CXXC domain (CXXC-3) that binds specifically to nonmethylated CpG, suggesting an explanation for methylation-independent localization. Transfection studies demonstrate that the CXXC-3 domain indeed targets nonmethylated CpG sites in vivo. Repression of nonmethylated reporter genes depends on the CXXC-3 domain, whereas repression of methylated reporters requires the MBD. Our findings indicate that MBD1 can interpret the CpG dinucleotide as a repressive signal in vivo regardless of its methylation status.\n" ], "offsets": [ [ 0, 1035 ] ] } ]

[ { "id": "PMID-15060159_T1", "type": "Protein", "text": [ "Mbd1" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-15060159_T2", "type": "Protein", "text": [ "MBD1" ], "offsets": [ [ 95, 99 ] ], "normalized": [] }, { "id": "PMID-15060159_T3", "type": "Protein", "text": [ "MBD1" ], "offsets": [ [ 251, 255 ] ], "normalized": [] }, { "id": "PMID-15060159_T4", "type": "Protein", "text": [ "Mbd1" ], "offsets": [ [ 365, 369 ] ], "normalized": [] }, { "id": "PMID-15060159_T5", "type": "Protein", "text": [ "Mbd1a" ], "offsets": [ [ 485, 490 ] ], "normalized": [] }, { "id": "PMID-15060159_T6", "type": "Protein", "text": [ "MBD1" ], "offsets": [ [ 926, 930 ] ], "normalized": [] } ]

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[ { "id": "PMID-15064827__text", "type": "abstract", "text": [ "Recombinant human zona pellucida proteins ZP1, ZP2 and ZP3 co-expressed in a human cell line. \nAIM: To produce biologically active recombinant human (rh) ZP proteins in a human cell for use in sperm function tests. METHODS: The human embryonic kidney cell line 293T was employed to produce rhZP1, rhZP2 and rhZP3 proteins individually and together by co-expression. Presence of these proteins in the culture medium and cell lysate was assessed by Western blotting analysis. The effect of the recombinant proteins on the human AR was assessed. RESULTS: RhZP2 and rhZP3 were secreted into the culture medium, whereas rhZP1 was found only in the cell lysate. Interestingly, when all zona pellucida proteins were co-expressed in the same cells, rhZP1 was also secreted into the culture medium. However, despite the presence of all three ZP proteins in sufficient concentration and evidence of heavy glycosylation on gel electrophoresis, biological activity to induce the AR was not observed. CONCLUSION: RhZP1, rhZP2 and rhZP3 were successfully expressed in the human embryonic kidney cell line 293T. It appears that an interaction amongst these proteins may be required for release of rhZP1 from the cell. Although this approach is not satisfactory for producing active human ZP proteins, it makes a significant contribution to the understanding of the structural and functional characteristics of the ZP proteins.\n" ], "offsets": [ [ 0, 1412 ] ] } ]

[ { "id": "PMID-15064827_T1", "type": "Protein", "text": [ "ZP1" ], "offsets": [ [ 42, 45 ] ], "normalized": [] }, { "id": "PMID-15064827_T2", "type": "Protein", "text": [ "ZP2" ], "offsets": [ [ 47, 50 ] ], "normalized": [] }, { "id": "PMID-15064827_T3", "type": "Protein", "text": [ "ZP3" ], "offsets": [ [ 55, 58 ] ], "normalized": [] }, { "id": "PMID-15064827_T4", "type": "Protein", "text": [ "ZP1" ], "offsets": [ [ 292, 295 ] ], "normalized": [] }, { "id": "PMID-15064827_T5", "type": "Protein", "text": [ "ZP2" ], "offsets": [ [ 299, 302 ] ], "normalized": [] }, { "id": "PMID-15064827_T6", "type": "Protein", "text": [ "ZP3" ], "offsets": [ [ 309, 312 ] ], "normalized": [] }, { "id": "PMID-15064827_T7", "type": "Protein", "text": [ "ZP2" ], "offsets": [ [ 554, 557 ] ], "normalized": [] }, { "id": "PMID-15064827_T8", "type": "Protein", "text": [ "ZP3" ], "offsets": [ [ 564, 567 ] ], "normalized": [] }, { "id": "PMID-15064827_T9", "type": "Protein", "text": [ "ZP1" ], "offsets": [ [ 617, 620 ] ], "normalized": [] }, { "id": "PMID-15064827_T10", "type": "Protein", "text": [ "ZP1" ], "offsets": [ [ 743, 746 ] ], "normalized": [] }, { "id": "PMID-15064827_T11", "type": "Protein", "text": [ "ZP1" ], "offsets": [ [ 1002, 1005 ] ], "normalized": [] }, { "id": "PMID-15064827_T12", "type": "Protein", "text": [ "ZP2" ], "offsets": [ [ 1009, 1012 ] ], "normalized": [] }, { "id": "PMID-15064827_T13", "type": "Protein", "text": [ "ZP3" ], "offsets": [ [ 1019, 1022 ] ], "normalized": [] }, { "id": "PMID-15064827_T14", "type": "Protein", "text": [ "ZP1" ], "offsets": [ [ 1184, 1187 ] ], "normalized": [] } ]

[]

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[]

[ { "id": "PMID-15084514__text", "type": "abstract", "text": [ "Leu-574 of human HIF-1alpha is a molecular determinant of prolyl hydroxylation. \nHypoxia-inducible factor (HIF)-1alpha, a master regulator of oxygen homeostasis, regulates genes crucial for cell growth and survival. In normoxia, HIF-1alpha is constantly degraded via the ubiquitin-proteasome pathway. The von Hippel-Lindau (VHL) E3 ubiquitin ligase binds HIF-1alpha through specific recognition of hydroxylated Pro-402 or Pro-564, both of which are modified by the oxygen-dependent HIF prolyl hydroxylases (PHDs/HPHs). Despite the identification of a conserved Leu-X-X-Leu-Ala-Pro motif, the molecular requirement of HIF-1alpha for PHDs/HPHs binding remains elusive. Recently, we demonstrated that Leu-574 of human HIF-1alpha--10 residues downstream of Pro-564--is essential for VHL recognition. We show here that the role of Leu-574 is to recruit PHD2/HPH2 for Pro-564 hydroxylation. An antibody specific for hydroxylated Pro-564 has been used to determine the hydroxylation status; mutation or deletion of Leu-574 results in a significant decrease in the ratio of the hydroxylated HIF-1alpha to the total amount. The nine-residue spacing between Pro-564 and Leu-574 is not obligatory for prolyl hydroxylation. Furthermore, mutation of Leu-574 disrupts the binding of PHD2/HPH2, a key prolyl hydroxylase for oxygen-dependent proteolysis of HIF-1alpha. Hence, our findings indicate that Leu-574 is essential for recruiting PHD2/HPH2, thereby providing a molecular basis for modulating HIF-1alpha activity.\n" ], "offsets": [ [ 0, 1506 ] ] } ]

[ { "id": "PMID-15084514_T1", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 17, 27 ] ], "normalized": [] }, { "id": "PMID-15084514_T2", "type": "Protein", "text": [ "Hypoxia-inducible factor (HIF)-1alpha" ], "offsets": [ [ 81, 118 ] ], "normalized": [] }, { "id": "PMID-15084514_T3", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 229, 239 ] ], "normalized": [] }, { "id": "PMID-15084514_T4", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 271, 280 ] ], "normalized": [] }, { "id": "PMID-15084514_T5", "type": "Protein", "text": [ "von Hippel-Lindau" ], "offsets": [ [ 305, 322 ] ], "normalized": [] }, { "id": "PMID-15084514_T6", "type": "Protein", "text": [ "VHL" ], "offsets": [ [ 324, 327 ] ], "normalized": [] }, { "id": "PMID-15084514_T7", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 332, 341 ] ], "normalized": [] }, { "id": "PMID-15084514_T8", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 355, 365 ] ], "normalized": [] }, { "id": "PMID-15084514_T9", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 617, 627 ] ], "normalized": [] }, { "id": "PMID-15084514_T10", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 715, 725 ] ], "normalized": [] }, { "id": "PMID-15084514_T11", "type": "Protein", "text": [ "VHL" ], "offsets": [ [ 779, 782 ] ], "normalized": [] }, { "id": "PMID-15084514_T12", "type": "Protein", "text": [ "PHD2" ], "offsets": [ [ 848, 852 ] ], "normalized": [] }, { "id": "PMID-15084514_T13", "type": "Protein", "text": [ "HPH2" ], "offsets": [ [ 853, 857 ] ], "normalized": [] }, { "id": "PMID-15084514_T14", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1083, 1093 ] ], "normalized": [] }, { "id": "PMID-15084514_T15", "type": "Protein", "text": [ "PHD2" ], "offsets": [ [ 1269, 1273 ] ], "normalized": [] }, { "id": "PMID-15084514_T16", "type": "Protein", "text": [ "HPH2" ], "offsets": [ [ 1274, 1278 ] ], "normalized": [] }, { "id": "PMID-15084514_T17", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1341, 1351 ] ], "normalized": [] }, { "id": "PMID-15084514_T18", "type": "Protein", "text": [ "PHD2" ], "offsets": [ [ 1423, 1427 ] ], "normalized": [] }, { "id": "PMID-15084514_T19", "type": "Protein", "text": [ "HPH2" ], "offsets": [ [ 1428, 1432 ] ], "normalized": [] }, { "id": "PMID-15084514_T20", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1485, 1495 ] ], "normalized": [] }, { "id": "PMID-15084514_T22", "type": "Entity", "text": [ "Pro-402" ], "offsets": [ [ 411, 418 ] ], "normalized": [] }, { "id": "PMID-15084514_T23", "type": "Entity", "text": [ "Pro-564" ], "offsets": [ [ 422, 429 ] ], "normalized": [] }, { "id": "PMID-15084514_T24", "type": "Entity", "text": [ "Pro-564" ], "offsets": [ [ 862, 869 ] ], "normalized": [] }, { "id": "PMID-15084514_T28", "type": "Entity", "text": [ "Pro-564" ], "offsets": [ [ 923, 930 ] ], "normalized": [] }, { "id": "PMID-15084514_T30", "type": "Entity", "text": [ "prolyl" ], "offsets": [ [ 1190, 1196 ] ], "normalized": [] } ]

[ { "id": "PMID-15084514_E1", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylated" ], "offsets": [ [ 398, 410 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15084514_T8" }, { "role": "Site", "ref_id": "PMID-15084514_T22" } ] }, { "id": "PMID-15084514_E2", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylated" ], "offsets": [ [ 398, 410 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15084514_T8" }, { "role": "Site", "ref_id": "PMID-15084514_T23" } ] }, { "id": "PMID-15084514_E3", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 870, 883 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15084514_T10" }, { "role": "Site", "ref_id": "PMID-15084514_T24" } ] }, { "id": "PMID-15084514_E4", "type": "Catalysis", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 870, 883 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15084514_E3" }, { "role": "Cause", "ref_id": "PMID-15084514_T12" } ] }, { "id": "PMID-15084514_E5", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylated" ], "offsets": [ [ 910, 922 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15084514_T14" }, { "role": "Site", "ref_id": "PMID-15084514_T28" } ] }, { "id": "PMID-15084514_E6", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylated" ], "offsets": [ [ 1070, 1082 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15084514_T14" } ] }, { "id": "PMID-15084514_E7", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 1197, 1210 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15084514_T14" }, { "role": "Site", "ref_id": "PMID-15084514_T30" } ] } ]

[ { "id": "PMID-15084514_1", "entity_ids": [ "PMID-15084514_T5", "PMID-15084514_T6" ] }, { "id": "PMID-15084514_2", "entity_ids": [ "PMID-15084514_T12", "PMID-15084514_T13" ] }, { "id": "PMID-15084514_3", "entity_ids": [ "PMID-15084514_T15", "PMID-15084514_T16" ] }, { "id": "PMID-15084514_4", "entity_ids": [ "PMID-15084514_T18", "PMID-15084514_T19" ] } ]

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[ { "id": "PMID-15118342__text", "type": "abstract", "text": [ "Transferrin microheterogeneity in fetal blood. \nOBJECTIVES: To investigate the distribution of microheterogeneous subfractions of transferrin in fetal blood and the influence of highly sialylated transferrins on fetal growth. STUDY METHOD: Serum transferrin concentrations were determined by a standard turbidimetric assay. Microheterogeneous transferrin subfractions were assessed by crossed immunoisoelectric focusing. RESULTS: In normal term infants, total serum transferrin concentrations and percent distribution of highly sialylated transferrins (> or = 5-sialo-transferrins) were markedly lower; the percent distributions of hyposialylated transferrins (0- and 1-sialo-transferrins) were apparently higher than those in non-pregnant and pregnant women. There was no significant positive correlation between the serum concentrations of total transferrin or highly sialylated transferrins in infants' blood and birth weights (r = 0.187, p = 0.582; r = 0.374, p = 0.257, respectively). CONCLUSION: The transferrin microheterogeneity pattern shifted towards reduced glycosylation and sialylation in addition to a decrease in total transferrin concentration in fetal blood compared to that of non-pregnant and pregnant women. The concentrations of serum total transferrin and the highly sialylated transferrins in fetal blood, if higher than a certain level, did not seem to have any influence on normal fetal growth.\n" ], "offsets": [ [ 0, 1420 ] ] } ]

[ { "id": "PMID-15118342_T1", "type": "Protein", "text": [ "Transferrin" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "PMID-15118342_T2", "type": "Protein", "text": [ "transferrin" ], "offsets": [ [ 130, 141 ] ], "normalized": [] }, { "id": "PMID-15118342_T3", "type": "Protein", "text": [ "transferrins" ], "offsets": [ [ 196, 208 ] ], "normalized": [] }, { "id": "PMID-15118342_T4", "type": "Protein", "text": [ "transferrin" ], "offsets": [ [ 246, 257 ] ], "normalized": [] }, { "id": "PMID-15118342_T5", "type": "Protein", "text": [ "transferrin" ], "offsets": [ [ 343, 354 ] ], "normalized": [] }, { "id": "PMID-15118342_T6", "type": "Protein", "text": [ "transferrin" ], "offsets": [ [ 466, 477 ] ], "normalized": [] }, { "id": "PMID-15118342_T7", "type": "Protein", "text": [ "transferrins" ], "offsets": [ [ 539, 551 ] ], "normalized": [] }, { "id": "PMID-15118342_T8", "type": "Protein", "text": [ "transferrins" ], "offsets": [ [ 568, 580 ] ], "normalized": [] }, { "id": "PMID-15118342_T9", "type": "Protein", "text": [ "transferrins" ], "offsets": [ [ 647, 659 ] ], "normalized": [] }, { "id": "PMID-15118342_T10", "type": "Protein", "text": [ "transferrins" ], "offsets": [ [ 676, 688 ] ], "normalized": [] }, { "id": "PMID-15118342_T11", "type": "Protein", "text": [ "transferrin" ], "offsets": [ [ 848, 859 ] ], "normalized": [] }, { "id": "PMID-15118342_T12", "type": "Protein", "text": [ "transferrins" ], "offsets": [ [ 881, 893 ] ], "normalized": [] }, { "id": "PMID-15118342_T13", "type": "Protein", "text": [ "transferrin" ], "offsets": [ [ 1006, 1017 ] ], "normalized": [] }, { "id": "PMID-15118342_T14", "type": "Protein", "text": [ "transferrin" ], "offsets": [ [ 1134, 1145 ] ], "normalized": [] }, { "id": "PMID-15118342_T15", "type": "Protein", "text": [ "transferrin" ], "offsets": [ [ 1262, 1273 ] ], "normalized": [] }, { "id": "PMID-15118342_T16", "type": "Protein", "text": [ "transferrins" ], "offsets": [ [ 1300, 1312 ] ], "normalized": [] } ]

[ { "id": "PMID-15118342_E1", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 1069, 1082 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15118342_T13" } ] } ]

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[]

[ { "id": "PMID-15128874__text", "type": "abstract", "text": [ "Heterochromatin and tri-methylated lysine 20 of histone H4 in animals. \nTri-methylated lysine 20 on histone H4 (Me(3)K20H4) is a marker of constitutive heterochromatin in murine interphase and metaphase cells. Heterochromatin marked by Me(3)K20H4 replicates late during S phase of the cell cycle. Serum starvation increases the number of cells that exhibit high levels of Me(3)K20H4 at constitutive heterochromatin. Me(3)K20H4 is also present at the centromeric heterochromatin of most meiotic chromosomes during spermatogenesis and at the pseudoautosomal region, as well as at some telomeres. It is not present on the XY-body. During murine embryogenesis the maternal pronucleus contains Me(3)K20H4; Me(3)K20H4 is absent from the paternal pronucleus. On Drosophila polytene chromosomes Me(3)K20H4 is present in a 'punctate pattern' at many chromosomal bands, including the chromocenter. In coccids it is present on the facultatively heterochromatinised paternal chromosome set. We also present evidence that Me(3)K20H4 is dependent upon H3-specific Suv(3)9 histone methyltransferase activity, suggesting that there may be 'epigenetic cross-talk' between histones H3 and H4.\n" ], "offsets": [ [ 0, 1175 ] ] } ]

[ { "id": "PMID-15128874_T1", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 48, 58 ] ], "normalized": [] }, { "id": "PMID-15128874_T2", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 100, 110 ] ], "normalized": [] }, { "id": "PMID-15128874_T3", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 120, 122 ] ], "normalized": [] }, { "id": "PMID-15128874_T4", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 244, 246 ] ], "normalized": [] }, { "id": "PMID-15128874_T5", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 380, 382 ] ], "normalized": [] }, { "id": "PMID-15128874_T6", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 424, 426 ] ], "normalized": [] }, { "id": "PMID-15128874_T7", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 697, 699 ] ], "normalized": [] }, { "id": "PMID-15128874_T8", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 709, 711 ] ], "normalized": [] }, { "id": "PMID-15128874_T9", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 795, 797 ] ], "normalized": [] }, { "id": "PMID-15128874_T10", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 1017, 1019 ] ], "normalized": [] }, { "id": "PMID-15128874_T11", "type": "Protein", "text": [ "H3-specific Suv(3)9 histone methyltransferase" ], "offsets": [ [ 1038, 1083 ] ], "normalized": [] }, { "id": "PMID-15128874_T12", "type": "Protein", "text": [ "histones H3" ], "offsets": [ [ 1155, 1166 ] ], "normalized": [] }, { "id": "PMID-15128874_T13", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 1171, 1173 ] ], "normalized": [] }, { "id": "PMID-15128874_T15", "type": "Entity", "text": [ "lysine 20" ], "offsets": [ [ 35, 44 ] ], "normalized": [] }, { "id": "PMID-15128874_T17", "type": "Entity", "text": [ "lysine 20" ], "offsets": [ [ 87, 96 ] ], "normalized": [] } ]

[ { "id": "PMID-15128874_E1", "type": "Methylation", "trigger": { "text": [ "tri-methylated" ], "offsets": [ [ 20, 34 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15128874_T1" }, { "role": "Site", "ref_id": "PMID-15128874_T15" } ] }, { "id": "PMID-15128874_E2", "type": "Methylation", "trigger": { "text": [ "Tri-methylated" ], "offsets": [ [ 72, 86 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15128874_T2" }, { "role": "Site", "ref_id": "PMID-15128874_T17" } ] } ]

[]

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[ { "id": "PMID-15175259__text", "type": "abstract", "text": [ "The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. \nThe covalent modification of nucleosomal histones has emerged as a major determinant of chromatin structure and gene activity. To understand the interplay between various histone modifications, including acetylation and methylation, we performed a genome-wide chromatin structure analysis in a higher eukaryote. We found a binary pattern of histone modifications among euchromatic genes, with active genes being hyperacetylated for H3 and H4 and hypermethylated at Lys 4 and Lys 79 of H3, and inactive genes being hypomethylated and deacetylated at the same residues. Furthermore, the degree of modification correlates with the level of transcription, and modifications are largely restricted to transcribed regions, suggesting that their regulation is tightly linked to polymerase activity.\n" ], "offsets": [ [ 0, 913 ] ] } ]

[ { "id": "PMID-15175259_T1", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 4, 11 ] ], "normalized": [] }, { "id": "PMID-15175259_T2", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 162, 170 ] ], "normalized": [] }, { "id": "PMID-15175259_T3", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 292, 299 ] ], "normalized": [] }, { "id": "PMID-15175259_T4", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 462, 469 ] ], "normalized": [] }, { "id": "PMID-15175259_T5", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 553, 555 ] ], "normalized": [] }, { "id": "PMID-15175259_T6", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 560, 562 ] ], "normalized": [] }, { "id": "PMID-15175259_T7", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 606, 608 ] ], "normalized": [] }, { "id": "PMID-15175259_T12", "type": "Entity", "text": [ "Lys 4" ], "offsets": [ [ 586, 591 ] ], "normalized": [] }, { "id": "PMID-15175259_T13", "type": "Entity", "text": [ "Lys 79" ], "offsets": [ [ 596, 602 ] ], "normalized": [] } ]

[ { "id": "PMID-15175259_E1", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 325, 336 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15175259_T3" } ] }, { "id": "PMID-15175259_E2", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 341, 352 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15175259_T3" } ] }, { "id": "PMID-15175259_E3", "type": "Acetylation", "trigger": { "text": [ "hyperacetylated" ], "offsets": [ [ 533, 548 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15175259_T5" } ] }, { "id": "PMID-15175259_E4", "type": "Acetylation", "trigger": { "text": [ "hyperacetylated" ], "offsets": [ [ 533, 548 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15175259_T6" } ] }, { "id": "PMID-15175259_E5", "type": "Methylation", "trigger": { "text": [ "hypermethylated" ], "offsets": [ [ 567, 582 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15175259_T7" }, { "role": "Site", "ref_id": "PMID-15175259_T12" } ] }, { "id": "PMID-15175259_E6", "type": "Methylation", "trigger": { "text": [ "hypermethylated" ], "offsets": [ [ 567, 582 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15175259_T7" }, { "role": "Site", "ref_id": "PMID-15175259_T13" } ] }, { "id": "PMID-15175259_E7", "type": "Methylation", "trigger": { "text": [ "hypomethylated" ], "offsets": [ [ 635, 649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15175259_T7" }, { "role": "Site", "ref_id": "PMID-15175259_T12" } ] }, { "id": "PMID-15175259_E8", "type": "Methylation", "trigger": { "text": [ "hypomethylated" ], "offsets": [ [ 635, 649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15175259_T7" }, { "role": "Site", "ref_id": "PMID-15175259_T13" } ] }, { "id": "PMID-15175259_E9", "type": "Deacetylation", "trigger": { "text": [ "deacetylated" ], "offsets": [ [ 654, 666 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15175259_T5" } ] }, { "id": "PMID-15175259_E10", "type": "Deacetylation", "trigger": { "text": [ "deacetylated" ], "offsets": [ [ 654, 666 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15175259_T6" } ] } ]

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[ { "id": "PMID-15201975__text", "type": "abstract", "text": [ "Less frequent promoter hypermethylation of DLC-1 gene in primary breast cancers. \nAbsence or low expression of DLC-1, a tumor suppressor gene, in breast cancers has been shown recently. LOH of 8p12-p22, on which DLC-1 is located, is frequent in breast cancers, but the correlation between low expression of DLC-1 and LOH has not been confirmed. To determine the implication of aberrant methylation, one of the most frequent mechanisms of silencing the tumor suppressor or cancer-related genes, we examined the methylation status of DLC-1 promoter region in breast cancer cell lines and primary breast tumors. The hypermethylation status was examined by MSP and 25% of cell lines harbored a methylated allele. The gene silencing by methylation was also confirmed by the re-expression of DLC-1 by the 5-aza-2'-deoxycytidine treatment in DLC-1 hypermethylated cell line. But the methylation of DLC-1 gene was less frequently shown in primary breast cancers (10%). These data suggest that hypermethylation is responsible for silencing of DLC-1 gene in a limited portion of breast cancers.\n" ], "offsets": [ [ 0, 1085 ] ] } ]

[ { "id": "PMID-15201975_T1", "type": "Protein", "text": [ "DLC-1" ], "offsets": [ [ 43, 48 ] ], "normalized": [] }, { "id": "PMID-15201975_T2", "type": "Protein", "text": [ "DLC-1" ], "offsets": [ [ 111, 116 ] ], "normalized": [] }, { "id": "PMID-15201975_T3", "type": "Protein", "text": [ "DLC-1" ], "offsets": [ [ 212, 217 ] ], "normalized": [] }, { "id": "PMID-15201975_T4", "type": "Protein", "text": [ "DLC-1" ], "offsets": [ [ 307, 312 ] ], "normalized": [] }, { "id": "PMID-15201975_T5", "type": "Protein", "text": [ "DLC-1" ], "offsets": [ [ 532, 537 ] ], "normalized": [] }, { "id": "PMID-15201975_T6", "type": "Protein", "text": [ "DLC-1" ], "offsets": [ [ 786, 791 ] ], "normalized": [] }, { "id": "PMID-15201975_T7", "type": "Protein", "text": [ "DLC-1" ], "offsets": [ [ 835, 840 ] ], "normalized": [] }, { "id": "PMID-15201975_T8", "type": "Protein", "text": [ "DLC-1" ], "offsets": [ [ 891, 896 ] ], "normalized": [] }, { "id": "PMID-15201975_T9", "type": "Protein", "text": [ "DLC-1" ], "offsets": [ [ 1034, 1039 ] ], "normalized": [] }, { "id": "PMID-15201975_T10", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 14, 22 ] ], "normalized": [] }, { "id": "PMID-15201975_T13", "type": "Entity", "text": [ "promoter region" ], "offsets": [ [ 538, 553 ] ], "normalized": [] } ]

[ { "id": "PMID-15201975_E1", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylation" ], "offsets": [ [ 23, 39 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15201975_T1" }, { "role": "Site", "ref_id": "PMID-15201975_T10" } ] }, { "id": "PMID-15201975_E2", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 510, 521 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15201975_T5" }, { "role": "Site", "ref_id": "PMID-15201975_T13" } ] }, { "id": "PMID-15201975_E3", "type": "DNA_methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 690, 700 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15201975_T5" }, { "role": "Site", "ref_id": "PMID-15201975_T13" } ] }, { "id": "PMID-15201975_E4", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylated" ], "offsets": [ [ 841, 856 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15201975_T7" } ] }, { "id": "PMID-15201975_E5", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 876, 887 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15201975_T8" } ] }, { "id": "PMID-15201975_E6", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylation" ], "offsets": [ [ 985, 1001 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15201975_T9" } ] } ]

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[ { "id": "PMID-15279588__text", "type": "abstract", "text": [ "Glycosylation of the ENV spike of primate immunodeficiency viruses and antibody neutralization. \nNeutralizing antibody titers have been correlated with protection following vaccination against many viral pathogens. The logical target of protective antibody responses elicited by potential HIV vaccines should be the viral Env spike on the surface of the virion. However, the potency and titers of neutralizing antibodies that arise during HIV infection are generally discouragingly low and the antibodies that do arise recognize mainly autologous virus. This is thought to be a result of a combination of immunodominance of hypervariable regions of the Env protein that can easily escape neutralization, antibody reactivity to gp160 \"decoy\" protein in cell surface debris or monomeric gp120, conformational constraints within the Env trimer that create unfavorable antibody binding conditions and extensive glycosylation of the exposed regions of Env within the trimer. This review will describe current knowledge regarding glycosylation as a mechanism of neutralization resistance and discuss experimental approaches used to overcome this resistance. Part of the strategy toward development of an optimally immunogenic Env spike will likely require modification of Env glycosylation.\n" ], "offsets": [ [ 0, 1285 ] ] } ]

[ { "id": "PMID-15279588_T1", "type": "Protein", "text": [ "ENV" ], "offsets": [ [ 21, 24 ] ], "normalized": [] }, { "id": "PMID-15279588_T2", "type": "Protein", "text": [ "Env" ], "offsets": [ [ 322, 325 ] ], "normalized": [] }, { "id": "PMID-15279588_T3", "type": "Protein", "text": [ "Env" ], "offsets": [ [ 653, 656 ] ], "normalized": [] }, { "id": "PMID-15279588_T4", "type": "Protein", "text": [ "gp160" ], "offsets": [ [ 727, 732 ] ], "normalized": [] }, { "id": "PMID-15279588_T5", "type": "Protein", "text": [ "gp120" ], "offsets": [ [ 785, 790 ] ], "normalized": [] }, { "id": "PMID-15279588_T6", "type": "Protein", "text": [ "Env" ], "offsets": [ [ 830, 833 ] ], "normalized": [] }, { "id": "PMID-15279588_T7", "type": "Protein", "text": [ "Env" ], "offsets": [ [ 947, 950 ] ], "normalized": [] }, { "id": "PMID-15279588_T8", "type": "Protein", "text": [ "Env" ], "offsets": [ [ 1220, 1223 ] ], "normalized": [] }, { "id": "PMID-15279588_T9", "type": "Protein", "text": [ "Env" ], "offsets": [ [ 1266, 1269 ] ], "normalized": [] } ]

[ { "id": "PMID-15279588_E1", "type": "Glycosylation", "trigger": { "text": [ "Glycosylation" ], "offsets": [ [ 0, 13 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15279588_T1" } ] }, { "id": "PMID-15279588_E2", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 907, 920 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15279588_T7" } ] }, { "id": "PMID-15279588_E3", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 1270, 1283 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15279588_T9" } ] } ]

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[ { "id": "PMID-15334633__text", "type": "abstract", "text": [ "Comparison of methylation-specific polymerase chain reaction (MSP) with reverse transcriptase-polymerase chain reaction (RT-PCR) in peripheral blood of gastric cancer patients. \nBACKGROUND AND OBJECTIVES: To achieve a complete cure in gastric cancer, primary and recurrent tumors must be detected at an early stage. This study was designed to compare carcinoembryonic antigen (CEA)-specific reverse transcriptase-polymerase chain reaction (RT-PCR) and methylation-specific polymerase chain reaction (MSP) for p16, E-cadherin, and retinoic acid receptor beta (RARbeta) genes using blood samples from gastric cancer patients. METHODS: Preoperative blood samples obtained from 41 patients with gastric cancer, including 9 with early-stage disease, and were subjected to RT-PCR and MSP assays. RESULTS: Ten of 41 (24%) patients exhibited a CEA-specific signal by RT-PCR. Positive rates were 11, 13, 50, and 50% in stages I, II, III, and IV, respectively. A significant association was found between RT-PCR results and stage (P< 0.01). The MSP assay detected hypermethylation of p16 in 9 patients (22%), E-cadherin in 9 patients (22%), and RARbeta in 6 patients (15%). Altogether, 18 patients (44%) showed hypermethylation. The positive rates were 37, 50, 40, and 75% in stages I, II, III, and IV, respectively. A significant association was found between aberrant methylation and venous invasion (P< 0.05). Neither the CEA-specific signal nor hypermethylation was detected in serum from control volunteers. CONCLUSIONS: The detection rate of MSP was higher than that of RT-PCR in gastric cancer. Both assays can serve as markers that allow selection of those cases requiring more intensive screening and aggressive postoperative treatment.\n" ], "offsets": [ [ 0, 1736 ] ] } ]

[ { "id": "PMID-15334633_T1", "type": "Protein", "text": [ "reverse transcriptase" ], "offsets": [ [ 72, 93 ] ], "normalized": [] }, { "id": "PMID-15334633_T2", "type": "Protein", "text": [ "reverse transcriptase" ], "offsets": [ [ 391, 412 ] ], "normalized": [] }, { "id": "PMID-15334633_T3", "type": "Protein", "text": [ "p16" ], "offsets": [ [ 509, 512 ] ], "normalized": [] }, { "id": "PMID-15334633_T4", "type": "Protein", "text": [ "E-cadherin" ], "offsets": [ [ 514, 524 ] ], "normalized": [] }, { "id": "PMID-15334633_T5", "type": "Protein", "text": [ "retinoic acid receptor beta" ], "offsets": [ [ 530, 557 ] ], "normalized": [] }, { "id": "PMID-15334633_T6", "type": "Protein", "text": [ "RARbeta" ], "offsets": [ [ 559, 566 ] ], "normalized": [] }, { "id": "PMID-15334633_T7", "type": "Protein", "text": [ "p16" ], "offsets": [ [ 1074, 1077 ] ], "normalized": [] }, { "id": "PMID-15334633_T8", "type": "Protein", "text": [ "E-cadherin" ], "offsets": [ [ 1099, 1109 ] ], "normalized": [] }, { "id": "PMID-15334633_T9", "type": "Protein", "text": [ "RARbeta" ], "offsets": [ [ 1135, 1142 ] ], "normalized": [] } ]

[ { "id": "PMID-15334633_E1", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylation" ], "offsets": [ [ 1054, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15334633_T7" } ] }, { "id": "PMID-15334633_E2", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylation" ], "offsets": [ [ 1054, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15334633_T8" } ] }, { "id": "PMID-15334633_E3", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylation" ], "offsets": [ [ 1054, 1070 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15334633_T9" } ] } ]

[ { "id": "PMID-15334633_1", "entity_ids": [ "PMID-15334633_T5", "PMID-15334633_T6" ] } ]

[]

[ { "id": "PMID-15336315__text", "type": "abstract", "text": [ "Superoxide dismutase and catalase are required to detect (.-)NO from both coupled and uncoupled neuronal no synthase. \nDespite numerous approaches to measuring nitric oxide ((.-)NO) formation from purified NO synthase (NOS), it is still not clear whether (.-)NO is a direct or indirect product of the NO synthase reaction. The direct detection of catalytically formed (.-)NO is complicated by side reactions with reactive oxide species like H(2)O(2) and superoxide. The aim of the present study was therefore to reinvestigate these reactions both electrochemically and by chemiluminescence detection with particular emphasis on the requirement for cofactors and their interference with (.-)NO detection. Flavins were found to generate large amounts of H(2)O(2) and were therefore excluded from subsequent incubations. Under conditions of both coupled and uncoupled catalysis, SOD was absolutely required to detect (.-)NO from NOS. H(2)O(2) formation took place also in the presence of SOD and gave a smaller yet significant interfering signal. Similar data were obtained when the proposed intermediate N(omega)-hydroxy-l-arginine was utilized as substrate. In conclusion, standard Clark-type ()NO electrodes are cross-sensitive to H(2)O(2) and therefore both SOD and catalase are absolutely required to specifically detect (.-)NO from NOS.\n" ], "offsets": [ [ 0, 1340 ] ] } ]

[ { "id": "PMID-15336315_T1", "type": "Protein", "text": [ "catalase" ], "offsets": [ [ 25, 33 ] ], "normalized": [] }, { "id": "PMID-15336315_T2", "type": "Protein", "text": [ "NO synthase" ], "offsets": [ [ 206, 217 ] ], "normalized": [] }, { "id": "PMID-15336315_T3", "type": "Protein", "text": [ "NOS" ], "offsets": [ [ 219, 222 ] ], "normalized": [] }, { "id": "PMID-15336315_T4", "type": "Protein", "text": [ "catalase" ], "offsets": [ [ 1267, 1275 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-15336315_1", "entity_ids": [ "PMID-15336315_T2", "PMID-15336315_T3" ] } ]

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[ { "id": "PMID-15358431__text", "type": "abstract", "text": [ "Widespread activation of antibiotic biosynthesis by S-adenosylmethionine in streptomycetes. \nThe effect of S-adenosylmethionine (SAM) on the production of various antibiotics was investigated to determine whether SAM-dependent methylation is required in biosynthetic pathways of antibiotics. Pristinamycin II(B) and granaticin do not require SAM-dependent methylation in their biosynthesis pathways, and production of these two antibiotics was increased about 2-fold when a low concentration (50 and 10 microM, respectively) of SAM was treated; in contrast, oleandomycin and avermectin B1a require SAM as a methyl donor in their biosynthesis, and production of these two antibiotics was increased 5-fold and 6-fold, depending on the SAM concentration within a certain range. We also found that the transcription of a pathway-specific regulator, gra-ORF9, was activated by exogenous SAM treatment. Production of oleandomycin and avermectin B1a was decreased by using a methyltransferase inhibitor, sinefungin, but the production levels of these antibiotics were restored to the control level by simultaneously adding SAM and sinefungin. Interestingly, we have found a similar stimulatory effect of S-adenosylhomocysteine (SAH), the methylation product of SAM, on antibiotic production in the four strains. Our results clearly demonstrate the widespread activation of antibiotic production using SAM in streptomycetes.\n" ], "offsets": [ [ 0, 1417 ] ] } ]

[ { "id": "PMID-15358431_T1", "type": "Protein", "text": [ "gra-ORF9" ], "offsets": [ [ 845, 853 ] ], "normalized": [] } ]

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[ { "id": "PMID-15383551__text", "type": "abstract", "text": [ "A phosphatidylserine-binding site in the cytosolic fragment of Clostridium sordellii lethal toxin facilitates glucosylation of membrane-bound Rac and is required for cytotoxicity. \nLarge clostridial toxins glucosylate some small G proteins on a threonine residue, thereby preventing their interactions with effector molecules and regulators. We show that the glucosyltransferase domain of lethal toxin from Clostridium sordellii (LT(cyt); amino acids 1-546), which is released into the cytosol during cell infection, binds preferentially to liposomes containing phosphatidylserine as compared with other anionic lipids. The binding of LT(cyt) to phosphatidylserine increases by two orders of magnitude the rate of glucosylation of liposome-bound geranyl-geranylated Rac-GDP. Limited proteolysis and deletion studies show that the binding site for phosphatidylserine lies within the first 18 N-terminal residues of LT(cyt). Deletion of these residues abolishes the effect of phosphatidylserine on the activity of LT(cyt) on liposome-bound geranyl-geranylated Rac-GDP and prevents the morphological effects induced by LT(cyt) microinjection into various cells, but it does not affect the intrinsic activity of LT(cyt) on non-geranyl-geranylated Rac-GDP in solution. We conclude that the avidity of LT(cyt) for phosphatidylserine facilitates its targeting to the cytosolic leaflet of cell membranes and, notably, the plasma membrane, where this anionic lipid is abundant and where several targets of lethal toxin reside.\n" ], "offsets": [ [ 0, 1518 ] ] } ]

[ { "id": "PMID-15383551_T1", "type": "Protein", "text": [ "LT(cyt)" ], "offsets": [ [ 430, 437 ] ], "normalized": [] }, { "id": "PMID-15383551_T2", "type": "Protein", "text": [ "LT(cyt)" ], "offsets": [ [ 635, 642 ] ], "normalized": [] }, { "id": "PMID-15383551_T3", "type": "Protein", "text": [ "LT(cyt)" ], "offsets": [ [ 914, 921 ] ], "normalized": [] }, { "id": "PMID-15383551_T4", "type": "Protein", "text": [ "LT(cyt)" ], "offsets": [ [ 1012, 1019 ] ], "normalized": [] }, { "id": "PMID-15383551_T5", "type": "Protein", "text": [ "LT(cyt)" ], "offsets": [ [ 1116, 1123 ] ], "normalized": [] }, { "id": "PMID-15383551_T6", "type": "Protein", "text": [ "LT(cyt)" ], "offsets": [ [ 1208, 1215 ] ], "normalized": [] }, { "id": "PMID-15383551_T7", "type": "Protein", "text": [ "LT(cyt)" ], "offsets": [ [ 1296, 1303 ] ], "normalized": [] } ]

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[]

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[ { "id": "PMID-1540579__text", "type": "abstract", "text": [ "Arginine residues as stabilizing elements in proteins. \nSite-specific substitutions of arginine for lysine in the thermostable D-xylose isomerase (XI) from Actinoplanes missouriensis are shown to impart significant heat stability enhancement in the presence of sugar substrates most probably by interfering with nonenzymatic glycation. The same substitutions are also found to increase heat stability in the absence of any sugar derivatives, where a mechanism based on prevention of glycation can no longer be invoked. This rather conservative substitution is moreover shown to improve thermostability in two other structurally unrelated proteins, human copper, zinc-superoxide dismutase (CuZnSOD) and D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Bacillus subtilis. The stabilizing effect of Lys----Arg substitutions is rationalized on the basis of a detailed analysis of the crystal structures of wild-type XI and of engineered variants with Lys----Arg substitution at four distinct locations, residues 253, 309, 319, and 323. Molecular model building analysis of the structures of wild-type and mutant CuZnSOD (K9R) and GAPDH (G281K and G281R) is used to explain the observed stability enhancement in these proteins. In addition to demonstrating that even thermostable proteins can lend themselves to further stability improvement, our findings provide direct evidence that arginine residues are important stabilizing elements in proteins. Moreover, the stabilizing role of electrostatic interactions, particularly between subunits in oligomeric proteins, is documented.\n" ], "offsets": [ [ 0, 1584 ] ] } ]

[ { "id": "PMID-1540579_T1", "type": "Protein", "text": [ "D-xylose isomerase" ], "offsets": [ [ 127, 145 ] ], "normalized": [] }, { "id": "PMID-1540579_T2", "type": "Protein", "text": [ "XI" ], "offsets": [ [ 147, 149 ] ], "normalized": [] }, { "id": "PMID-1540579_T3", "type": "Protein", "text": [ "copper, zinc-superoxide dismutase" ], "offsets": [ [ 654, 687 ] ], "normalized": [] }, { "id": "PMID-1540579_T4", "type": "Protein", "text": [ "CuZnSOD" ], "offsets": [ [ 689, 696 ] ], "normalized": [] }, { "id": "PMID-1540579_T5", "type": "Protein", "text": [ "D-glyceraldehyde-3-phosphate dehydrogenase" ], "offsets": [ [ 702, 744 ] ], "normalized": [] }, { "id": "PMID-1540579_T6", "type": "Protein", "text": [ "GAPDH" ], "offsets": [ [ 746, 751 ] ], "normalized": [] }, { "id": "PMID-1540579_T7", "type": "Protein", "text": [ "XI" ], "offsets": [ [ 919, 921 ] ], "normalized": [] }, { "id": "PMID-1540579_T8", "type": "Protein", "text": [ "CuZnSOD" ], "offsets": [ [ 1115, 1122 ] ], "normalized": [] }, { "id": "PMID-1540579_T9", "type": "Protein", "text": [ "GAPDH" ], "offsets": [ [ 1133, 1138 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-1540579_1", "entity_ids": [ "PMID-1540579_T1", "PMID-1540579_T2" ] }, { "id": "PMID-1540579_2", "entity_ids": [ "PMID-1540579_T3", "PMID-1540579_T4" ] }, { "id": "PMID-1540579_3", "entity_ids": [ "PMID-1540579_T5", "PMID-1540579_T6" ] } ]

[]

[ { "id": "PMID-15485929__text", "type": "abstract", "text": [ "Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes. \nProtein arginine methyltransferases (PRMTs) have been implicated in transcriptional activation and repression, but their role in controlling cell growth and proliferation remains obscure. We have recently shown that PRMT5 can interact with flag-tagged BRG1- and hBRM-based hSWI/SNF chromatin remodelers and that both complexes can specifically methylate histones H3 and H4. Here we report that PRMT5 can be found in association with endogenous hSWI/SNF complexes, which can methylate H3 and H4 N-terminal tails, and show that H3 arginine 8 and H4 arginine 3 are preferred sites of methylation by recombinant and hSWI/SNF-associated PRMT5. To elucidate the role played by PRMT5 in gene regulation, we have established a PRMT5 antisense cell line and determined by microarray analysis that more genes are derepressed when PRMT5 levels are reduced. Among the affected genes, we show that suppressor of tumorigenicity 7 (ST7) and nonmetastatic 23 (NM23) are direct targets of PRMT5-containing BRG1 and hBRM complexes. Furthermore, we demonstrate that expression of ST7 and NM23 is reduced in a cell line that overexpresses PRMT5 and that this decrease in expression correlates with H3R8 methylation, H3K9 deacetylation, and increased transformation of NIH 3T3 cells. These findings suggest that the BRG1- and hBRM-associated PRMT5 regulates cell growth and proliferation by controlling expression of genes involved in tumor suppression.\n" ], "offsets": [ [ 0, 1574 ] ] } ]

[ { "id": "PMID-15485929_T1", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 25, 30 ] ], "normalized": [] }, { "id": "PMID-15485929_T2", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 42, 52 ] ], "normalized": [] }, { "id": "PMID-15485929_T3", "type": "Protein", "text": [ "ST7" ], "offsets": [ [ 103, 106 ] ], "normalized": [] }, { "id": "PMID-15485929_T4", "type": "Protein", "text": [ "NM23" ], "offsets": [ [ 111, 115 ] ], "normalized": [] }, { "id": "PMID-15485929_T5", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 357, 362 ] ], "normalized": [] }, { "id": "PMID-15485929_T6", "type": "Protein", "text": [ "BRG1" ], "offsets": [ [ 393, 397 ] ], "normalized": [] }, { "id": "PMID-15485929_T7", "type": "Protein", "text": [ "BRM" ], "offsets": [ [ 404, 407 ] ], "normalized": [] }, { "id": "PMID-15485929_T8", "type": "Protein", "text": [ "histones H3" ], "offsets": [ [ 495, 506 ] ], "normalized": [] }, { "id": "PMID-15485929_T9", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 511, 513 ] ], "normalized": [] }, { "id": "PMID-15485929_T10", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 535, 540 ] ], "normalized": [] }, { "id": "PMID-15485929_T11", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 625, 627 ] ], "normalized": [] }, { "id": "PMID-15485929_T12", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 632, 634 ] ], "normalized": [] }, { "id": "PMID-15485929_T13", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 667, 669 ] ], "normalized": [] }, { "id": "PMID-15485929_T14", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 685, 687 ] ], "normalized": [] }, { "id": "PMID-15485929_T15", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 773, 778 ] ], "normalized": [] }, { "id": "PMID-15485929_T16", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 812, 817 ] ], "normalized": [] }, { "id": "PMID-15485929_T17", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 860, 865 ] ], "normalized": [] }, { "id": "PMID-15485929_T18", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 961, 966 ] ], "normalized": [] }, { "id": "PMID-15485929_T19", "type": "Protein", "text": [ "suppressor of tumorigenicity 7" ], "offsets": [ [ 1026, 1056 ] ], "normalized": [] }, { "id": "PMID-15485929_T20", "type": "Protein", "text": [ "ST7" ], "offsets": [ [ 1058, 1061 ] ], "normalized": [] }, { "id": "PMID-15485929_T21", "type": "Protein", "text": [ "nonmetastatic 23" ], "offsets": [ [ 1067, 1083 ] ], "normalized": [] }, { "id": "PMID-15485929_T22", "type": "Protein", "text": [ "NM23" ], "offsets": [ [ 1085, 1089 ] ], "normalized": [] }, { "id": "PMID-15485929_T23", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 1113, 1118 ] ], "normalized": [] }, { "id": "PMID-15485929_T24", "type": "Protein", "text": [ "BRG1" ], "offsets": [ [ 1130, 1134 ] ], "normalized": [] }, { "id": "PMID-15485929_T25", "type": "Protein", "text": [ "BRM" ], "offsets": [ [ 1140, 1143 ] ], "normalized": [] }, { "id": "PMID-15485929_T26", "type": "Protein", "text": [ "ST7" ], "offsets": [ [ 1202, 1205 ] ], "normalized": [] }, { "id": "PMID-15485929_T27", "type": "Protein", "text": [ "NM23" ], "offsets": [ [ 1210, 1214 ] ], "normalized": [] }, { "id": "PMID-15485929_T28", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 1260, 1265 ] ], "normalized": [] }, { "id": "PMID-15485929_T29", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1319, 1321 ] ], "normalized": [] }, { "id": "PMID-15485929_T30", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1337, 1339 ] ], "normalized": [] }, { "id": "PMID-15485929_T31", "type": "Protein", "text": [ "BRG1" ], "offsets": [ [ 1436, 1440 ] ], "normalized": [] }, { "id": "PMID-15485929_T32", "type": "Protein", "text": [ "BRM" ], "offsets": [ [ 1447, 1450 ] ], "normalized": [] }, { "id": "PMID-15485929_T33", "type": "Protein", "text": [ "PRMT5" ], "offsets": [ [ 1462, 1467 ] ], "normalized": [] }, { "id": "PMID-15485929_T36", "type": "Entity", "text": [ "arginine 8" ], "offsets": [ [ 53, 63 ] ], "normalized": [] }, { "id": "PMID-15485929_T38", "type": "Entity", "text": [ "arginine 8" ], "offsets": [ [ 670, 680 ] ], "normalized": [] }, { "id": "PMID-15485929_T39", "type": "Entity", "text": [ "arginine 3" ], "offsets": [ [ 688, 698 ] ], "normalized": [] }, { "id": "PMID-15485929_T42", "type": "Entity", "text": [ "R8" ], "offsets": [ [ 1321, 1323 ] ], "normalized": [] }, { "id": "PMID-15485929_T44", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 1339, 1341 ] ], "normalized": [] } ]

[ { "id": "PMID-15485929_E1", "type": "Methylation", "trigger": { "text": [ "methylates" ], "offsets": [ [ 31, 41 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_T2" }, { "role": "Site", "ref_id": "PMID-15485929_T36" }, { "role": "Contextgene", "ref_id": "PMID-15485929_T3" } ] }, { "id": "PMID-15485929_E2", "type": "Methylation", "trigger": { "text": [ "methylates" ], "offsets": [ [ 31, 41 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_T2" }, { "role": "Site", "ref_id": "PMID-15485929_T36" }, { "role": "Contextgene", "ref_id": "PMID-15485929_T4" } ] }, { "id": "PMID-15485929_E3", "type": "Catalysis", "trigger": { "text": [ "methylates" ], "offsets": [ [ 31, 41 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_E2" }, { "role": "Cause", "ref_id": "PMID-15485929_T1" } ] }, { "id": "PMID-15485929_E4", "type": "Catalysis", "trigger": { "text": [ "methylates" ], "offsets": [ [ 31, 41 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_E1" }, { "role": "Cause", "ref_id": "PMID-15485929_T1" } ] }, { "id": "PMID-15485929_E5", "type": "Methylation", "trigger": { "text": [ "methylate" ], "offsets": [ [ 485, 494 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_T8" } ] }, { "id": "PMID-15485929_E6", "type": "Methylation", "trigger": { "text": [ "methylate" ], "offsets": [ [ 485, 494 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_T9" } ] }, { "id": "PMID-15485929_E7", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 722, 733 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_T13" }, { "role": "Site", "ref_id": "PMID-15485929_T38" } ] }, { "id": "PMID-15485929_E8", "type": "Catalysis", "trigger": { "text": [ "methylation" ], "offsets": [ [ 722, 733 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_E7" }, { "role": "Cause", "ref_id": "PMID-15485929_T15" } ] }, { "id": "PMID-15485929_E9", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 722, 733 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_T14" }, { "role": "Site", "ref_id": "PMID-15485929_T39" } ] }, { "id": "PMID-15485929_E10", "type": "Catalysis", "trigger": { "text": [ "methylation" ], "offsets": [ [ 722, 733 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_E9" }, { "role": "Cause", "ref_id": "PMID-15485929_T15" } ] }, { "id": "PMID-15485929_E11", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1324, 1335 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_T29" }, { "role": "Site", "ref_id": "PMID-15485929_T42" }, { "role": "Contextgene", "ref_id": "PMID-15485929_T27" } ] }, { "id": "PMID-15485929_E12", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1324, 1335 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_T29" }, { "role": "Site", "ref_id": "PMID-15485929_T42" }, { "role": "Contextgene", "ref_id": "PMID-15485929_T26" } ] }, { "id": "PMID-15485929_E13", "type": "Deacetylation", "trigger": { "text": [ "deacetylation" ], "offsets": [ [ 1342, 1355 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_T30" }, { "role": "Site", "ref_id": "PMID-15485929_T44" }, { "role": "Contextgene", "ref_id": "PMID-15485929_T26" } ] }, { "id": "PMID-15485929_E14", "type": "Deacetylation", "trigger": { "text": [ "deacetylation" ], "offsets": [ [ 1342, 1355 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15485929_T30" }, { "role": "Site", "ref_id": "PMID-15485929_T44" }, { "role": "Contextgene", "ref_id": "PMID-15485929_T27" } ] } ]

[ { "id": "PMID-15485929_1", "entity_ids": [ "PMID-15485929_T19", "PMID-15485929_T20" ] }, { "id": "PMID-15485929_2", "entity_ids": [ "PMID-15485929_T21", "PMID-15485929_T22" ] } ]

[]

[ { "id": "PMID-15522198__text", "type": "abstract", "text": [ "Sex- and tissue-specific expression of maintenance and de novo DNA methyltransferases upon low dose X-irradiation in mice. \nDNA methylation is crucial for normal development, proliferation, and proper maintenance of genome stability for a given organism. A variety of DNA damaging agents that are known to affect genome stability were also shown to alter DNA methylation patterns. We have recently pioneered the studies in the area of the radiation effects on DNA methylation, and found that radiation exposure led to substantial dose-dependent and tissue-specific DNA hypomethylation, which was much more pronounced in spleen and liver of female animals. The exact mechanisms of radiation-induced DNA hypomethylation are still to be uncovered. We have previously shown that one of those mechanisms may potentially be DNA repair related. Another possible mechanism may be linked to changes in the expression of DNA methyltransferases (DNMTs). In the current study, we examined the radiation-induced changes in expression of maintenance DNMT1, and de novo methyltransferases DNMT3a and DNMT3b in spleen and liver of irradiated animals. This was paralleled by the studies of acute and chronic IR-induced methylation changes in spleen and liver of intact animals, as well as in animals with altered sex hormone status. Here we report that radiation-induced DNA methylation changes correlated with radiation-induced alterations in expression of DNA methyltransferases. We present the data on tissue-specificity in radiation-induced expression of DNA methyltransferases, and prove that changes in the expression of de novo methyltransferases DNMT3a and DNMT3b are the most important in radiation-induced DNA methylation alterations. We also discuss the role of sex hormones, especially estrogen, in the generation of the sex-specific radiation-induced methylation changes.\n" ], "offsets": [ [ 0, 1868 ] ] } ]

[ { "id": "PMID-15522198_T1", "type": "Protein", "text": [ "DNMT1" ], "offsets": [ [ 1036, 1041 ] ], "normalized": [] }, { "id": "PMID-15522198_T2", "type": "Protein", "text": [ "DNMT3a" ], "offsets": [ [ 1074, 1080 ] ], "normalized": [] }, { "id": "PMID-15522198_T3", "type": "Protein", "text": [ "DNMT3b" ], "offsets": [ [ 1085, 1091 ] ], "normalized": [] }, { "id": "PMID-15522198_T4", "type": "Protein", "text": [ "DNMT3a" ], "offsets": [ [ 1637, 1643 ] ], "normalized": [] }, { "id": "PMID-15522198_T5", "type": "Protein", "text": [ "DNMT3b" ], "offsets": [ [ 1648, 1654 ] ], "normalized": [] } ]

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[]

[]

[ { "id": "PMID-15574921__text", "type": "abstract", "text": [ "Characterization of a novel amylolytic enzyme encoded by a gene from a soil-derived metagenomic library. \nIt has been estimated that less than 1% of the microorganisms in nature can be cultivated by conventional techniques. Thus, the classical approach of isolating enzymes from pure cultures allows the analysis of only a subset of the total naturally occurring microbiota in environmental samples enriched in microorganisms. To isolate useful microbial enzymes from uncultured soil microorganisms, a metagenome was isolated from soil samples, and a metagenomic library was constructed by using the pUC19 vector. The library was screened for amylase activity, and one clone from among approximately 30,000 recombinant Escherichia coli clones showed amylase activity. Sequencing of the clone revealed a novel amylolytic enzyme expressed from a novel gene. The putative amylase gene (amyM) was overexpressed and purified for characterization. Optimal conditions for the enzyme activity of the AmyM protein were 42 degrees C and pH 9.0; Ca2+ stabilized the activity. The amylase hydrolyzed soluble starch and cyclodextrins to produce high levels of maltose and hydrolyzed pullulan to panose. The enzyme showed a high transglycosylation activity, making alpha-(1, 4) linkages exclusively. The hydrolysis and transglycosylation properties of AmyM suggest that it has novel characteristics and can be regarded as an intermediate type of maltogenic amylase, alpha-amylase, and 4-alpha-glucanotransferase.\n" ], "offsets": [ [ 0, 1499 ] ] } ]

[ { "id": "PMID-15574921_T1", "type": "Protein", "text": [ "amyM" ], "offsets": [ [ 883, 887 ] ], "normalized": [] }, { "id": "PMID-15574921_T2", "type": "Protein", "text": [ "AmyM" ], "offsets": [ [ 992, 996 ] ], "normalized": [] }, { "id": "PMID-15574921_T3", "type": "Protein", "text": [ "AmyM" ], "offsets": [ [ 1338, 1342 ] ], "normalized": [] }, { "id": "PMID-15574921_T4", "type": "Protein", "text": [ "4-alpha-glucanotransferase" ], "offsets": [ [ 1471, 1497 ] ], "normalized": [] } ]

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[ { "id": "PMID-15581571__text", "type": "abstract", "text": [ "4-Hydroxyphenylpyruvate dioxygenase. \n4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an Fe(II)-dependent, non-heme oxygenase that catalyzes the conversion of 4-hydroxyphenylpyruvate to homogentisate. This reaction involves decarboxylation, substituent migration and aromatic oxygenation in a single catalytic cycle. HPPD is a member of the alpha-keto acid dependent oxygenases that typically require an alpha-keto acid (almost exclusively alpha-ketoglutarate) and molecular oxygen to either oxygenate or oxidize a third molecule. As an exception in this class of enzymes HPPD has only two substrates, does not use alpha-ketoglutarate, and incorporates both atoms of dioxygen into the aromatic product, homogentisate. The tertiary structure of the enzyme would suggest that its mechanism converged with that of other alpha-keto acid enzymes from an extradiol dioxygenase progenitor. The transformation catalyzed by HPPD has both agricultural and therapeutic significance. HPPD catalyzes the second step in the pathway for the catabolism of tyrosine, that is common to essentially all aerobic forms of life. In plants this pathway has an anabolic branch from homogentisate that forms essential isoprenoid redox cofactors such as plastoquinone and tocopherol. Naturally occurring multi-ketone molecules act as allelopathic agents by inhibiting HPPD and preventing the production of homogentisate and hence required redox cofactors. This has been the basis for the development of a range of very effective herbicides that are currently used commercially. In humans, deficiencies of specific enzymes of the tyrosine catabolism pathway give rise to a number of severe metabolic disorders. Interestingly, HPPD inhibitor/herbicide molecules act also as therapeutic agents for a number of debilitating and lethal inborn defects in tyrosine catabolism by preventing the accumulation of toxic metabolites.\n" ], "offsets": [ [ 0, 1894 ] ] } ]

[ { "id": "PMID-15581571_T1", "type": "Protein", "text": [ "4-Hydroxyphenylpyruvate dioxygenase" ], "offsets": [ [ 0, 35 ] ], "normalized": [] }, { "id": "PMID-15581571_T2", "type": "Protein", "text": [ "4-Hydroxyphenylpyruvate dioxygenase" ], "offsets": [ [ 38, 73 ] ], "normalized": [] }, { "id": "PMID-15581571_T3", "type": "Protein", "text": [ "HPPD" ], "offsets": [ [ 75, 79 ] ], "normalized": [] }, { "id": "PMID-15581571_T4", "type": "Protein", "text": [ "HPPD" ], "offsets": [ [ 315, 319 ] ], "normalized": [] }, { "id": "PMID-15581571_T5", "type": "Protein", "text": [ "HPPD" ], "offsets": [ [ 570, 574 ] ], "normalized": [] }, { "id": "PMID-15581571_T6", "type": "Protein", "text": [ "HPPD" ], "offsets": [ [ 913, 917 ] ], "normalized": [] }, { "id": "PMID-15581571_T7", "type": "Protein", "text": [ "HPPD" ], "offsets": [ [ 970, 974 ] ], "normalized": [] }, { "id": "PMID-15581571_T8", "type": "Protein", "text": [ "HPPD" ], "offsets": [ [ 1340, 1344 ] ], "normalized": [] }, { "id": "PMID-15581571_T9", "type": "Protein", "text": [ "HPPD" ], "offsets": [ [ 1697, 1701 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-15581571_1", "entity_ids": [ "PMID-15581571_T2", "PMID-15581571_T3" ] } ]

[]

[ { "id": "PMID-15581869__text", "type": "abstract", "text": [ "Distinct dynamics and distribution of histone methyl-lysine derivatives in mouse development. \nHistone methylation acts as an epigenetic regulator of chromatin activity through the modification of arginine and lysine residues on histones H3 and H4. In the case of lysine, this includes the formation of mono-, di-, or trimethyl groups, each of which is presumed to represent a distinct functional state at the cellular level. To examine the potential developmental roles of these modifications, we determined the global patterns of lysine methylation involving K9 on histone H3 and K20 on histone H4 in midgestation mouse embryos. For each lysine target site, we observed distinct subnuclear distributions of the mono- and trimethyl versions in 10T1/2 cells that were conserved within primary cultures and within the 3D-tissue architecture of the embryo. Interestingly, three of these modifications, histone H3 trimethyl K9, histone H4 monomethyl K20, and histone H4 trimethyl K20 exhibited marked differences in their distribution within the neuroepithelium. Specifically, both histone H3 trimethyl K9 and H4 monomethyl K20 were elevated in proliferating cells of the neural tube, which in the case of the K9 modification was limited to mitotic cells on the luminal surface. In contrast, histone H4 trimethyl K20 was progressively lost from these medial regions and became enriched in differentiating neurons in the ventrolateral neural tube. The inverse relationship of histone H4 K20 methyl derivatives is even more striking during skeletal and cardiac myogenesis where the accumulation of the trimethyl modification in pericentromeric heterochromatin suggests a role in gene silencing in postmitotic muscle cells. Importantly, our results establish that histone lysine methylation occurs in a highly dynamic manner that is consistent with their function in an epigenetic program for cell division and differentiation.\n" ], "offsets": [ [ 0, 1922 ] ] } ]

[ { "id": "PMID-15581869_T1", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 38, 45 ] ], "normalized": [] }, { "id": "PMID-15581869_T2", "type": "Protein", "text": [ "Histone" ], "offsets": [ [ 95, 102 ] ], "normalized": [] }, { "id": "PMID-15581869_T3", "type": "Protein", "text": [ "histones H3" ], "offsets": [ [ 229, 240 ] ], "normalized": [] }, { "id": "PMID-15581869_T4", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 245, 247 ] ], "normalized": [] }, { "id": "PMID-15581869_T5", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 567, 577 ] ], "normalized": [] }, { "id": "PMID-15581869_T6", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 589, 599 ] ], "normalized": [] }, { "id": "PMID-15581869_T7", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 900, 910 ] ], "normalized": [] }, { "id": "PMID-15581869_T8", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 925, 935 ] ], "normalized": [] }, { "id": "PMID-15581869_T9", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 956, 966 ] ], "normalized": [] }, { "id": "PMID-15581869_T10", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 1079, 1089 ] ], "normalized": [] }, { "id": "PMID-15581869_T11", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 1107, 1109 ] ], "normalized": [] }, { "id": "PMID-15581869_T12", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 1289, 1299 ] ], "normalized": [] }, { "id": "PMID-15581869_T13", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 1472, 1482 ] ], "normalized": [] }, { "id": "PMID-15581869_T14", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1758, 1765 ] ], "normalized": [] }, { "id": "PMID-15581869_T16", "type": "Entity", "text": [ "arginine" ], "offsets": [ [ 197, 205 ] ], "normalized": [] }, { "id": "PMID-15581869_T17", "type": "Entity", "text": [ "lysine" ], "offsets": [ [ 210, 216 ] ], "normalized": [] }, { "id": "PMID-15581869_T19", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 561, 563 ] ], "normalized": [] }, { "id": "PMID-15581869_T20", "type": "Entity", "text": [ "K20" ], "offsets": [ [ 582, 585 ] ], "normalized": [] }, { "id": "PMID-15581869_T22", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 921, 923 ] ], "normalized": [] }, { "id": "PMID-15581869_T23", "type": "Entity", "text": [ "K20" ], "offsets": [ [ 947, 950 ] ], "normalized": [] }, { "id": "PMID-15581869_T24", "type": "Entity", "text": [ "K20" ], "offsets": [ [ 977, 980 ] ], "normalized": [] }, { "id": "PMID-15581869_T25", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 1207, 1209 ] ], "normalized": [] }, { "id": "PMID-15581869_T27", "type": "Entity", "text": [ "K20" ], "offsets": [ [ 1483, 1486 ] ], "normalized": [] }, { "id": "PMID-15581869_T29", "type": "Entity", "text": [ "lysine" ], "offsets": [ [ 1766, 1772 ] ], "normalized": [] } ]

[ { "id": "PMID-15581869_E1", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 103, 114 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15581869_T3" }, { "role": "Site", "ref_id": "PMID-15581869_T16" } ] }, { "id": "PMID-15581869_E2", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 103, 114 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15581869_T3" }, { "role": "Site", "ref_id": "PMID-15581869_T17" } ] }, { "id": "PMID-15581869_E3", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 103, 114 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15581869_T4" }, { "role": "Site", "ref_id": "PMID-15581869_T16" } ] }, { "id": "PMID-15581869_E4", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 103, 114 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15581869_T4" }, { "role": "Site", "ref_id": "PMID-15581869_T17" } ] }, { "id": "PMID-15581869_E5", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 539, 550 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15581869_T5" }, { "role": "Site", "ref_id": "PMID-15581869_T19" } ] }, { "id": "PMID-15581869_E6", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 539, 550 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15581869_T6" }, { "role": "Site", "ref_id": "PMID-15581869_T20" } ] }, { "id": "PMID-15581869_E7", "type": "Methylation", "trigger": { "text": [ "modifications" ], "offsets": [ [ 885, 898 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15581869_T8" }, { "role": "Site", "ref_id": "PMID-15581869_T23" } ] }, { "id": "PMID-15581869_E8", "type": "Methylation", "trigger": { "text": [ "modifications" ], "offsets": [ [ 885, 898 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15581869_T9" }, { "role": "Site", "ref_id": "PMID-15581869_T24" } ] }, { "id": "PMID-15581869_E9", "type": "Methylation", "trigger": { "text": [ "modifications" ], "offsets": [ [ 885, 898 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15581869_T7" }, { "role": "Site", "ref_id": "PMID-15581869_T22" } ] }, { "id": "PMID-15581869_E10", "type": "Methylation", "trigger": { "text": [ "modification" ], "offsets": [ [ 1210, 1222 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15581869_T10" }, { "role": "Site", "ref_id": "PMID-15581869_T25" } ] }, { "id": "PMID-15581869_E11", "type": "Methylation", "trigger": { "text": [ "trimethyl modification" ], "offsets": [ [ 1597, 1619 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15581869_T13" }, { "role": "Site", "ref_id": "PMID-15581869_T27" } ] }, { "id": "PMID-15581869_E12", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1773, 1784 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15581869_T14" }, { "role": "Site", "ref_id": "PMID-15581869_T29" } ] } ]

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[ { "id": "PMID-15589118__text", "type": "abstract", "text": [ "Decreased expression of lysyl hydroxylase 2 (LH2) in skin fibroblasts from three Ehlers-Danlos patients does not result from mutations in either the coding or proximal promoter region of the LH2 gene. \nThe Ehlers-Danlos syndromes (EDS) are a heterogeneous group of inherited connective tissue disorders characterized by tissue fragility, hyperelasticity of the skin and joint hypermobility. This phenotype, accompanied by kyphoscoliosis and/or ocular fragility, is present in patients with the autosomal recessive type VI form of EDS. These patients have significantly decreased levels of lysyl hydroxylase (LH) activity, due to mutations in the LH1 gene. LH hydroxylates specific lysine residues in the collagen molecule that are precursors for the formation of cross-links which provide collagen with its tensile strength. No disorder has been directly linked to decreased expression of LH2 and LH3, two other isoforms of LH. This study describes 3 patients with mixed phenotypes of EDS, who have significantly decreased mRNAs for LH2, but normal levels of LH1 and LH3 mRNAs, in their skin fibroblasts. In contrast to the effect of LH1 deficiency in EDS VI patients, the decreased expression of LH2 does not affect LH activity, bifunctional collagen cross-links (measured after reduction as dihydroxylysinonorleucine (DHLNL) and hydroxylysinonorleucine (HLNL)), or helical lysine hydroxylation in these cell lines. Sequence analysis of full length LH2 cDNAs and 1kb of the promoter region of LH2 does not show mutations that could explain the decreased expression of LH2. These results suggest that the deficiency of LH2 in these fibroblasts may be caused by changes in other factors required for the expression of LH2.\n" ], "offsets": [ [ 0, 1722 ] ] } ]

[ { "id": "PMID-15589118_T1", "type": "Protein", "text": [ "lysyl hydroxylase 2" ], "offsets": [ [ 24, 43 ] ], "normalized": [] }, { "id": "PMID-15589118_T2", "type": "Protein", "text": [ "LH2" ], "offsets": [ [ 45, 48 ] ], "normalized": [] }, { "id": "PMID-15589118_T3", "type": "Protein", "text": [ "LH2" ], "offsets": [ [ 191, 194 ] ], "normalized": [] }, { "id": "PMID-15589118_T4", "type": "Protein", "text": [ "LH1" ], "offsets": [ [ 646, 649 ] ], "normalized": [] }, { "id": "PMID-15589118_T5", "type": "Protein", "text": [ "LH2" ], "offsets": [ [ 889, 892 ] ], "normalized": [] }, { "id": "PMID-15589118_T6", "type": "Protein", "text": [ "LH3" ], "offsets": [ [ 897, 900 ] ], "normalized": [] }, { "id": "PMID-15589118_T7", "type": "Protein", "text": [ "LH2" ], "offsets": [ [ 1033, 1036 ] ], "normalized": [] }, { "id": "PMID-15589118_T8", "type": "Protein", "text": [ "LH1" ], "offsets": [ [ 1059, 1062 ] ], "normalized": [] }, { "id": "PMID-15589118_T9", "type": "Protein", "text": [ "LH3" ], "offsets": [ [ 1067, 1070 ] ], "normalized": [] }, { "id": "PMID-15589118_T10", "type": "Protein", "text": [ "LH1" ], "offsets": [ [ 1134, 1137 ] ], "normalized": [] }, { "id": "PMID-15589118_T11", "type": "Protein", "text": [ "LH2" ], "offsets": [ [ 1197, 1200 ] ], "normalized": [] }, { "id": "PMID-15589118_T12", "type": "Protein", "text": [ "LH2" ], "offsets": [ [ 1450, 1453 ] ], "normalized": [] }, { "id": "PMID-15589118_T13", "type": "Protein", "text": [ "LH2" ], "offsets": [ [ 1494, 1497 ] ], "normalized": [] }, { "id": "PMID-15589118_T14", "type": "Protein", "text": [ "LH2" ], "offsets": [ [ 1569, 1572 ] ], "normalized": [] }, { "id": "PMID-15589118_T15", "type": "Protein", "text": [ "LH2" ], "offsets": [ [ 1619, 1622 ] ], "normalized": [] }, { "id": "PMID-15589118_T16", "type": "Protein", "text": [ "LH2" ], "offsets": [ [ 1717, 1720 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-15589118_1", "entity_ids": [ "PMID-15589118_T1", "PMID-15589118_T2" ] } ]

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[ { "id": "PMID-15590670__text", "type": "abstract", "text": [ "Expression and purification of functionally active hyaluronan-binding domains from human cartilage link protein, aggrecan and versican: formation of ternary complexes with defined hyaluronan oligosaccharides. \nThe chondroitin sulfate proteoglycan aggrecan forms link protein-stabilized complexes with hyaluronan (HA), via its N-terminal G1-domain, that provide cartilage with its load bearing properties. Similar aggregates (potentially containing new members of the link protein family), in which other chondroitin sulfate proteoglycans (i.e. versican, brevican, and neurocan) substitute for aggrecan, may contribute to the structural integrity of many other tissues including skin and brain. In this study, cartilage link protein (cLP) and the G1-domains of aggrecan (AG1) and versican (VG1) were expressed in Drosophila S2 cells. The recombinant human proteins were found to have properties similar to those described for the native molecules (e.g. cLP was able to form oligomers, and HA decasaccharides were the minimum size that could compete effectively for their binding to polymeric HA). Gel filtration and protein cross-linking/matrix-assisted laser desorption ionization time-of-flight peptide fingerprinting showed that cLP and AG1 interact in the absence or presence of HA. Conversely, cLP and VG1 did not bind directly to each other in solution yet formed ternary complexes with HA24. N-linked glycosylation of AG1 and VG1 was demonstrated to be unnecessary for either HA binding or the formation of ternary complexes. Surprisingly, the length of HA required to accommodate two G1-domains was found to be significantly larger for aggrecan than versican, which may reflect differences in the conformation of HA stabilized on binding these proteins.\n" ], "offsets": [ [ 0, 1761 ] ] } ]

[ { "id": "PMID-15590670_T1", "type": "Protein", "text": [ "aggrecan" ], "offsets": [ [ 113, 121 ] ], "normalized": [] }, { "id": "PMID-15590670_T2", "type": "Protein", "text": [ "versican" ], "offsets": [ [ 126, 134 ] ], "normalized": [] }, { "id": "PMID-15590670_T3", "type": "Protein", "text": [ "aggrecan" ], "offsets": [ [ 247, 255 ] ], "normalized": [] }, { "id": "PMID-15590670_T4", "type": "Protein", "text": [ "versican" ], "offsets": [ [ 544, 552 ] ], "normalized": [] }, { "id": "PMID-15590670_T5", "type": "Protein", "text": [ "brevican" ], "offsets": [ [ 554, 562 ] ], "normalized": [] }, { "id": "PMID-15590670_T6", "type": "Protein", "text": [ "neurocan" ], "offsets": [ [ 568, 576 ] ], "normalized": [] }, { "id": "PMID-15590670_T7", "type": "Protein", "text": [ "aggrecan" ], "offsets": [ [ 593, 601 ] ], "normalized": [] }, { "id": "PMID-15590670_T8", "type": "Protein", "text": [ "aggrecan" ], "offsets": [ [ 760, 768 ] ], "normalized": [] }, { "id": "PMID-15590670_T9", "type": "Protein", "text": [ "versican" ], "offsets": [ [ 779, 787 ] ], "normalized": [] }, { "id": "PMID-15590670_T10", "type": "Protein", "text": [ "aggrecan" ], "offsets": [ [ 1643, 1651 ] ], "normalized": [] }, { "id": "PMID-15590670_T11", "type": "Protein", "text": [ "versican" ], "offsets": [ [ 1657, 1665 ] ], "normalized": [] } ]

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[ { "id": "PMID-15610077__text", "type": "abstract", "text": [ "Protective mechanism of epigallocatechin-3-gallate against Helicobacter pylori-induced gastric epithelial cytotoxicity via the blockage of TLR-4 signaling. \nBACKGROUND: Helicobacter pylori infection leads to gastric mucosal damage by several mechanisms including the direct effect of virulence factors produced by H. pylori, propagation of inflammation, oxidative stress, DNA damage, and induction of apoptosis. (-)-Epigallocatechin-3-gallate (EGCG), one of the green tea catechins, is known to suppress H. pylori-induced gastritis through its antioxidative and antibacterial actions. In this study, we evaluated the protective mechanism of EGCG against H. pylori-induced cytotoxicity in gastric epithelial cells. MATERIALS AND METHODS: MTT assays and dye exclusion assays were performed to analyze the effect of EGCG on the viability of gastric epithelial cells. The degree of DNA damage was evaluated by Comet assay and apoptotic DNA fragmentation assay. To investigate the effect of EGCG on H. pylori-induced toll-like receptor 4 (TLR-4) signaling, reverse transcription-polymerase chain reaction and Western blot analysis corresponding to glycosylated TLR-4 were carried out. Lipoxygenase metabolites were measured with reverse-phase, high-performance liquid chromatography. RESULTS: EGCG pretreatment effectively rescued gastric mucosal cells from the H. pylori-induced apoptotic cell death and DNA damage, and administration of this catechin enhanced gastric epithelial cell proliferation. Helicobacter pylori infection stimulated the glycosylation of TLR-4, which initiates intracellular signaling in the infected host cell, but the pretreatment with EGCG completely blocked the TLR-4 glycosylation. The blockage of TLR-4 activation by EGCG resulted in inactivation of extracellular signal response kinase 1/2 and of nuclear factor-kappaB, the downstream molecules of TLR-4 signaling induced by H. pylori. This disturbance of H. pylori-induced host cell signaling by EGCG attenuated the synthesis of the proinflammatory mediator, hydroxyeicosatetraenoic acid. CONCLUSIONS: EGCG pretreatment showed significant cytoprotective effects against H. pylori-induced gastric cytotoxicity via interference of the TLR-4 signaling induced by H. pylori. Thus, our result implies that continuous intakes of green tea could prevent the deleterious consequences of H. pylori infection.\n" ], "offsets": [ [ 0, 2378 ] ] } ]

[ { "id": "PMID-15610077_T1", "type": "Protein", "text": [ "TLR-4" ], "offsets": [ [ 139, 144 ] ], "normalized": [] }, { "id": "PMID-15610077_T2", "type": "Protein", "text": [ "toll-like receptor 4" ], "offsets": [ [ 1012, 1032 ] ], "normalized": [] }, { "id": "PMID-15610077_T3", "type": "Protein", "text": [ "TLR-4" ], "offsets": [ [ 1034, 1039 ] ], "normalized": [] }, { "id": "PMID-15610077_T4", "type": "Protein", "text": [ "TLR-4" ], "offsets": [ [ 1156, 1161 ] ], "normalized": [] }, { "id": "PMID-15610077_T5", "type": "Protein", "text": [ "TLR-4" ], "offsets": [ [ 1558, 1563 ] ], "normalized": [] }, { "id": "PMID-15610077_T6", "type": "Protein", "text": [ "TLR-4" ], "offsets": [ [ 1686, 1691 ] ], "normalized": [] }, { "id": "PMID-15610077_T7", "type": "Protein", "text": [ "TLR-4" ], "offsets": [ [ 1723, 1728 ] ], "normalized": [] }, { "id": "PMID-15610077_T8", "type": "Protein", "text": [ "extracellular signal response kinase 1" ], "offsets": [ [ 1776, 1814 ] ], "normalized": [] }, { "id": "PMID-15610077_T9", "type": "Protein", "text": [ "2" ], "offsets": [ [ 1815, 1816 ] ], "normalized": [] }, { "id": "PMID-15610077_T10", "type": "Protein", "text": [ "TLR-4" ], "offsets": [ [ 1875, 1880 ] ], "normalized": [] }, { "id": "PMID-15610077_T11", "type": "Protein", "text": [ "TLR-4" ], "offsets": [ [ 2211, 2216 ] ], "normalized": [] } ]

[ { "id": "PMID-15610077_E1", "type": "Glycosylation", "trigger": { "text": [ "glycosylated" ], "offsets": [ [ 1143, 1155 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15610077_T4" } ] }, { "id": "PMID-15610077_E2", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 1541, 1554 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15610077_T5" } ] }, { "id": "PMID-15610077_E3", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 1692, 1705 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15610077_T6" } ] } ]

[ { "id": "PMID-15610077_1", "entity_ids": [ "PMID-15610077_T2", "PMID-15610077_T3" ] } ]

[]

[ { "id": "PMID-15625318__text", "type": "abstract", "text": [ "Bare-faced curassow lysozyme carrying amino acid substitutions at subsites E and F shows a change in activity against chitooligosaccharide caused by a local conformational change. \nA new form of avian lysozyme, bare-faced curassow lysozyme (BCL), was purified and chemically sequenced. Of the 26 substitutions relative to chicken lysozyme, three, F34Y, T47S, and R114H, are of substrate-interacting residues in the E and F subsites, which would contribute to the acceptor binding for transglycosylation. T47S is a novel substitution in this lysozyme class. While other lysozymes also have substitutions at positions 114 and 34, they also contain numerous others, including ones in the other substrate binding sites, A-D. Furthermore, T47S lies on the left side, while F34Y and R114H are located on the right side of the E-F subsites. BCL therefore should allow comparison of the independent contributions of these sites to substrate binding and transglycosylation. The activity toward the N-acetylglucosamine pentamer revealed that the substitutions at the E-F sites reduced the binding free energies at the E-F sites and the rate constant for transglycosylation without the conformation change of other substrate binding sites on the protein. MD simulation analysis of BCL suggested that the substituted amino acids changed the local conformation of this lysozyme at the E-F sites.\n" ], "offsets": [ [ 0, 1383 ] ] } ]

[ { "id": "PMID-15625318_T1", "type": "Protein", "text": [ "lysozyme" ], "offsets": [ [ 20, 28 ] ], "normalized": [] }, { "id": "PMID-15625318_T2", "type": "Protein", "text": [ "lysozyme" ], "offsets": [ [ 231, 239 ] ], "normalized": [] }, { "id": "PMID-15625318_T3", "type": "Protein", "text": [ "lysozyme" ], "offsets": [ [ 330, 338 ] ], "normalized": [] }, { "id": "PMID-15625318_T4", "type": "Protein", "text": [ "lysozyme" ], "offsets": [ [ 541, 549 ] ], "normalized": [] }, { "id": "PMID-15625318_T5", "type": "Protein", "text": [ "lysozymes" ], "offsets": [ [ 569, 578 ] ], "normalized": [] }, { "id": "PMID-15625318_T6", "type": "Protein", "text": [ "lysozyme" ], "offsets": [ [ 1356, 1364 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-15632065__text", "type": "abstract", "text": [ "Histone H2B ubiquitylation is associated with elongating RNA polymerase II. \nRad6-mediated ubiquitylation of histone H2B at lysine 123 has been linked to transcriptional activation and the regulation of lysine methylation on histone H3. However, how Rad6 and H2B ubiquitylation contribute to the transcription and histone methylation processes is poorly understood. Here, we show that the Paf1 transcription elongation complex and the E3 ligase for Rad6, Bre1, mediate an association of Rad6 with the hyperphosphorylated (elongating) form of RNA polymerase II (Pol II). This association appears to be necessary for the transcriptional activities of Rad6, as deletion of various Paf1 complex members or Bre1 abolishes H2B ubiquitylation (ubH2B) and reduces the recruitment of Rad6 to the promoters and transcribed regions of active genes. Using the inducible GAL1 gene as a model, we find that the recruitment of Rad6 upon activation occurs rapidly and transiently across the gene and coincides precisely with the appearance of Pol II. Significantly, during GAL1 activation in an rtf1 deletion mutant, Rad6 accumulates at the promoter but is absent from the transcribed region. This fact suggests that Rad6 is recruited to promoters independently of the Paf1 complex but then requires this complex for entrance into the coding region of genes in a Pol II-associated manner. In support of a role for Rad6-dependent H2B ubiquitylation in transcription elongation, we find that ubH2B levels are dramatically reduced in strains bearing mutations of the Pol II C-terminal domain (CTD) and abolished by inactivation of Kin28, the serine 5 CTD kinase that promotes the transition from initiation to elongation. Furthermore, synthetic genetic array analysis reveals that the Rad6 complex interacts genetically with a number of known or suspected transcription elongation factors. Finally, we show that Saccharomyces cerevisiae mutants bearing defects in the pathway to H2B ubiquitylation display transcription elongation defects as assayed by 6-azauracil sensitivity. Collectively, our results indicate a role for Rad6 and H2B ubiquitylation during the elongation cycle of transcription and suggest a mechanism by which H3 methylation may be regulated.\n" ], "offsets": [ [ 0, 2244 ] ] } ]

[ { "id": "PMID-15632065_T1", "type": "Protein", "text": [ "Histone H2B" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "PMID-15632065_T2", "type": "Protein", "text": [ "Rad6" ], "offsets": [ [ 77, 81 ] ], "normalized": [] }, { "id": "PMID-15632065_T3", "type": "Protein", "text": [ "histone H2B" ], "offsets": [ [ 109, 120 ] ], "normalized": [] }, { "id": "PMID-15632065_T4", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 225, 235 ] ], "normalized": [] }, { "id": "PMID-15632065_T5", "type": "Protein", "text": [ "Rad6" ], "offsets": [ [ 250, 254 ] ], "normalized": [] }, { "id": "PMID-15632065_T6", "type": "Protein", "text": [ "H2B" ], "offsets": [ [ 259, 262 ] ], "normalized": [] }, { "id": "PMID-15632065_T7", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 314, 321 ] ], "normalized": [] }, { "id": "PMID-15632065_T8", "type": "Protein", "text": [ "Paf1" ], "offsets": [ [ 389, 393 ] ], "normalized": [] }, { "id": "PMID-15632065_T9", "type": "Protein", "text": [ "Rad6" ], "offsets": [ [ 449, 453 ] ], "normalized": [] }, { "id": "PMID-15632065_T10", "type": "Protein", "text": [ "Bre1" ], "offsets": [ [ 455, 459 ] ], "normalized": [] }, { "id": "PMID-15632065_T11", "type": "Protein", "text": [ "Rad6" ], "offsets": [ [ 487, 491 ] ], "normalized": [] }, { "id": "PMID-15632065_T12", "type": "Protein", "text": [ "Rad6" ], "offsets": [ [ 649, 653 ] ], "normalized": [] }, { "id": "PMID-15632065_T13", "type": "Protein", "text": [ "Paf1" ], "offsets": [ [ 678, 682 ] ], "normalized": [] }, { "id": "PMID-15632065_T14", "type": "Protein", "text": [ "Bre1" ], "offsets": [ [ 702, 706 ] ], "normalized": [] }, { "id": "PMID-15632065_T15", "type": "Protein", "text": [ "H2B" ], "offsets": [ [ 717, 720 ] ], "normalized": [] }, { "id": "PMID-15632065_T16", "type": "Protein", "text": [ "H2B" ], "offsets": [ [ 739, 742 ] ], "normalized": [] }, { "id": "PMID-15632065_T17", "type": "Protein", "text": [ "Rad6" ], "offsets": [ [ 775, 779 ] ], "normalized": [] }, { "id": "PMID-15632065_T18", "type": "Protein", "text": [ "GAL1" ], "offsets": [ [ 858, 862 ] ], "normalized": [] }, { "id": "PMID-15632065_T19", "type": "Protein", "text": [ "Rad6" ], "offsets": [ [ 912, 916 ] ], "normalized": [] }, { "id": "PMID-15632065_T20", "type": "Protein", "text": [ "GAL1" ], "offsets": [ [ 1057, 1061 ] ], "normalized": [] }, { "id": "PMID-15632065_T21", "type": "Protein", "text": [ "rtf1" ], "offsets": [ [ 1079, 1083 ] ], "normalized": [] }, { "id": "PMID-15632065_T22", "type": "Protein", "text": [ "Rad6" ], "offsets": [ [ 1101, 1105 ] ], "normalized": [] }, { "id": "PMID-15632065_T23", "type": "Protein", "text": [ "Rad6" ], "offsets": [ [ 1201, 1205 ] ], "normalized": [] }, { "id": "PMID-15632065_T24", "type": "Protein", "text": [ "Paf1" ], "offsets": [ [ 1253, 1257 ] ], "normalized": [] }, { "id": "PMID-15632065_T25", "type": "Protein", "text": [ "Rad6" ], "offsets": [ [ 1398, 1402 ] ], "normalized": [] }, { "id": "PMID-15632065_T26", "type": "Protein", "text": [ "H2B" ], "offsets": [ [ 1413, 1416 ] ], "normalized": [] }, { "id": "PMID-15632065_T27", "type": "Protein", "text": [ "H2B" ], "offsets": [ [ 1476, 1479 ] ], "normalized": [] }, { "id": "PMID-15632065_T28", "type": "Protein", "text": [ "Kin28" ], "offsets": [ [ 1612, 1617 ] ], "normalized": [] }, { "id": "PMID-15632065_T29", "type": "Protein", "text": [ "Rad6" ], "offsets": [ [ 1766, 1770 ] ], "normalized": [] }, { "id": "PMID-15632065_T30", "type": "Protein", "text": [ "H2B" ], "offsets": [ [ 1960, 1963 ] ], "normalized": [] }, { "id": "PMID-15632065_T31", "type": "Protein", "text": [ "Rad6" ], "offsets": [ [ 2105, 2109 ] ], "normalized": [] }, { "id": "PMID-15632065_T32", "type": "Protein", "text": [ "H2B" ], "offsets": [ [ 2114, 2117 ] ], "normalized": [] }, { "id": "PMID-15632065_T33", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 2211, 2213 ] ], "normalized": [] }, { "id": "PMID-15632065_T36", "type": "Entity", "text": [ "lysine 123" ], "offsets": [ [ 124, 134 ] ], "normalized": [] }, { "id": "PMID-15632065_T37", "type": "Entity", "text": [ "lysine" ], "offsets": [ [ 203, 209 ] ], "normalized": [] } ]

[ { "id": "PMID-15632065_E1", "type": "Ubiquitination", "trigger": { "text": [ "ubiquitylation" ], "offsets": [ [ 12, 26 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15632065_T1" } ] }, { "id": "PMID-15632065_E2", "type": "Ubiquitination", "trigger": { "text": [ "ubiquitylation" ], "offsets": [ [ 91, 105 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15632065_T3" }, { "role": "Site", "ref_id": "PMID-15632065_T36" } ] }, { "id": "PMID-15632065_E3", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 210, 221 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15632065_T4" }, { "role": "Site", "ref_id": "PMID-15632065_T37" } ] }, { "id": "PMID-15632065_E4", "type": "Ubiquitination", "trigger": { "text": [ "ubiquitylation" ], "offsets": [ [ 263, 277 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15632065_T6" } ] }, { "id": "PMID-15632065_E5", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 322, 333 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15632065_T7" } ] }, { "id": "PMID-15632065_E6", "type": "Ubiquitination", "trigger": { "text": [ "ubiquitylation" ], "offsets": [ [ 721, 735 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15632065_T15" } ] }, { "id": "PMID-15632065_E7", "type": "Ubiquitination", "trigger": { "text": [ "ubiquitylation" ], "offsets": [ [ 1417, 1431 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15632065_T26" } ] }, { "id": "PMID-15632065_E8", "type": "Ubiquitination", "trigger": { "text": [ "ubiquitylation" ], "offsets": [ [ 1964, 1978 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15632065_T30" } ] }, { "id": "PMID-15632065_E9", "type": "Ubiquitination", "trigger": { "text": [ "ubiquitylation" ], "offsets": [ [ 2118, 2132 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15632065_T32" } ] }, { "id": "PMID-15632065_E10", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 2214, 2225 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15632065_T33" } ] } ]

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[]

[ { "id": "PMID-15632154__text", "type": "abstract", "text": [ "Glycosylation-related gene expression in prion diseases: PrPSc accumulation in scrapie infected GT1 cells depends on beta-1,4-linked GalNAc-4-SO4 hyposulfation. \nSeveral lines of evidence indicate that some glycoconjugates are efficient effectors of the cellular prion protein (PrP(C)) conversion into its pathogenic (PrP(Sc)) isoform. To assess how glycoconjugate glycan moieties participate in the biogenesis of PrP(Sc), an exhaustive comparative analysis of the expression of about 200 glycosylation-related genes was performed on prion-infected or not, hypothalamus-derived GT1 cells by hybridization of DNA microarrays, semiquantitative RT-PCR, and biochemical assays. A significant up- (30-fold) and down- (17-fold) regulation of the expression of the ChGn1 and Chst8 genes, respectively, was observed in prion-infected cells. ChGn1 and Chst8 are involved in the initiation of the synthesis of chondroitin sulfate and in the 4-O-sulfation of non-reducing N-acetylgalactosamine residues, respectively. A possible role for a hyposulfated chondroitin in PrP(Sc) accumulation was evidenced at the protein level and by determination of chondroitin and heparan sulfate amounts. Treatment of Sc-GT1 cells with a heparan mimetic (HM2602) induced an important reduction of the amount of PrP(Sc), associated with a total reversion of the transcription pattern of the N-acetylgalactosamine-4-O-sulfotransferase 8. It suggests a link between the genetic control of 4-O-sulfation and PrP(Sc) accumulation.\n" ], "offsets": [ [ 0, 1499 ] ] } ]

[ { "id": "PMID-15632154_T1", "type": "Protein", "text": [ "prion" ], "offsets": [ [ 41, 46 ] ], "normalized": [] }, { "id": "PMID-15632154_T2", "type": "Protein", "text": [ "PrPSc" ], "offsets": [ [ 57, 62 ] ], "normalized": [] }, { "id": "PMID-15632154_T3", "type": "Protein", "text": [ "prion protein" ], "offsets": [ [ 263, 276 ] ], "normalized": [] }, { "id": "PMID-15632154_T4", "type": "Protein", "text": [ "PrP(C)" ], "offsets": [ [ 278, 284 ] ], "normalized": [] }, { "id": "PMID-15632154_T5", "type": "Protein", "text": [ "PrP(Sc)" ], "offsets": [ [ 318, 325 ] ], "normalized": [] }, { "id": "PMID-15632154_T6", "type": "Protein", "text": [ "PrP(Sc)" ], "offsets": [ [ 414, 421 ] ], "normalized": [] }, { "id": "PMID-15632154_T7", "type": "Protein", "text": [ "prion" ], "offsets": [ [ 534, 539 ] ], "normalized": [] }, { "id": "PMID-15632154_T8", "type": "Protein", "text": [ "ChGn1" ], "offsets": [ [ 758, 763 ] ], "normalized": [] }, { "id": "PMID-15632154_T9", "type": "Protein", "text": [ "Chst8" ], "offsets": [ [ 768, 773 ] ], "normalized": [] }, { "id": "PMID-15632154_T10", "type": "Protein", "text": [ "prion" ], "offsets": [ [ 811, 816 ] ], "normalized": [] }, { "id": "PMID-15632154_T11", "type": "Protein", "text": [ "ChGn1" ], "offsets": [ [ 833, 838 ] ], "normalized": [] }, { "id": "PMID-15632154_T12", "type": "Protein", "text": [ "Chst8" ], "offsets": [ [ 843, 848 ] ], "normalized": [] }, { "id": "PMID-15632154_T13", "type": "Protein", "text": [ "PrP(Sc)" ], "offsets": [ [ 1057, 1064 ] ], "normalized": [] }, { "id": "PMID-15632154_T14", "type": "Protein", "text": [ "PrP(Sc)" ], "offsets": [ [ 1284, 1291 ] ], "normalized": [] }, { "id": "PMID-15632154_T15", "type": "Protein", "text": [ "N-acetylgalactosamine-4-O-sulfotransferase 8" ], "offsets": [ [ 1363, 1407 ] ], "normalized": [] }, { "id": "PMID-15632154_T16", "type": "Protein", "text": [ "PrP(Sc)" ], "offsets": [ [ 1477, 1484 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-15632154_1", "entity_ids": [ "PMID-15632154_T3", "PMID-15632154_T4" ] } ]

[]

[ { "id": "PMID-1566859__text", "type": "abstract", "text": [ "Expression and transport of rabbit surfactant protein A in COS-1 cells. \nSV40-transformed green monkey kidney (COS-1) cells were transfected with expression plasmids that contained either the structural gene or cDNA for surfactant protein A (SP-A), a major protein of rabbit lung surfactant. The transfected COS-1 cells synthesized several isoforms of SP-A that were found to be less acidic than those produced in rabbit lung tissue. SP-A species with apparent molecular weight (M(r)) approximately equal to 29,000-33,000 were detected in the transfected cells, whereas glycosylated forms with apparent M(r) approximately equal to 33,000-38,000 were detectable only in the culture medium. Analysis of transfected cells by indirect immunofluorescence revealed that SP-A was localized in punctate bodies throughout the cytoplasm. Expressed SP-A was not detectable on the cell surface nor was there evidence that secreted SP-A was endocytosed by COS-1 cells. After subcellular fractionation of the transfected COS-1 cells, SP-A was found to be localized predominantly in the 5,000- and 18,000-g pellet fractions; little or no immunoreactive SP-A was detectable in cytosolic fractions. Treatment of transfected cells with the glycosylation inhibitor tunicamycin prevented secretion of SP-A into the medium, suggesting a role of glycosylation in secretion of SP-A. On the other hand, treatment of transfected cells with inhibitors of proline hydroxylation, which may cause destabilization of the collagen-like domain of SP-A, reduced but did not prevent secretion of SP-A into the culture medium.(ABSTRACT TRUNCATED AT 250 WORDS)\n" ], "offsets": [ [ 0, 1625 ] ] } ]

[ { "id": "PMID-1566859_T1", "type": "Protein", "text": [ "surfactant protein A" ], "offsets": [ [ 35, 55 ] ], "normalized": [] }, { "id": "PMID-1566859_T2", "type": "Protein", "text": [ "surfactant protein A" ], "offsets": [ [ 220, 240 ] ], "normalized": [] }, { "id": "PMID-1566859_T3", "type": "Protein", "text": [ "SP-A" ], "offsets": [ [ 242, 246 ] ], "normalized": [] }, { "id": "PMID-1566859_T4", "type": "Protein", "text": [ "SP-A" ], "offsets": [ [ 352, 356 ] ], "normalized": [] }, { "id": "PMID-1566859_T5", "type": "Protein", "text": [ "SP-A" ], "offsets": [ [ 434, 438 ] ], "normalized": [] }, { "id": "PMID-1566859_T6", "type": "Protein", "text": [ "SP-A" ], "offsets": [ [ 764, 768 ] ], "normalized": [] }, { "id": "PMID-1566859_T7", "type": "Protein", "text": [ "SP-A" ], "offsets": [ [ 838, 842 ] ], "normalized": [] }, { "id": "PMID-1566859_T8", "type": "Protein", "text": [ "SP-A" ], "offsets": [ [ 919, 923 ] ], "normalized": [] }, { "id": "PMID-1566859_T9", "type": "Protein", "text": [ "SP-A" ], "offsets": [ [ 1020, 1024 ] ], "normalized": [] }, { "id": "PMID-1566859_T10", "type": "Protein", "text": [ "SP-A" ], "offsets": [ [ 1138, 1142 ] ], "normalized": [] }, { "id": "PMID-1566859_T11", "type": "Protein", "text": [ "SP-A" ], "offsets": [ [ 1281, 1285 ] ], "normalized": [] }, { "id": "PMID-1566859_T12", "type": "Protein", "text": [ "SP-A" ], "offsets": [ [ 1354, 1358 ] ], "normalized": [] }, { "id": "PMID-1566859_T13", "type": "Protein", "text": [ "SP-A" ], "offsets": [ [ 1515, 1519 ] ], "normalized": [] }, { "id": "PMID-1566859_T14", "type": "Protein", "text": [ "SP-A" ], "offsets": [ [ 1562, 1566 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-1568251__text", "type": "abstract", "text": [ "Histone H4 isoforms acetylated at specific lysine residues define individual chromosomes and chromatin domains in Drosophila polytene nuclei. \nHistone H4 isoforms acetylated at lysines 5, 8, 12, or 16 have been shown, by indirect immunofluorescence with site-specific antisera, to have distinct patterns of distribution in interphase, polytene chromosomes from Drosophila larvae. H4 molecules acetylated at lysines 5 or 8 are distributed in overlapping, but nonidentical, islands throughout the euchromatic chromosome arms. beta-Heterochromatin in the chromocenter is depleted in these isoforms, but relatively enriched in H4 acetylated at lysine 12. H4 acetylated at lysine 16 is found at numerous sites along the transcriptionally hyperactive X chromosome in male larvae, but not in male autosomes or any chromosome in female cells. These findings support the hypothesis that H4 molecules acetylated at particular sites mediate unique and specific effects on chromatin function.\n" ], "offsets": [ [ 0, 981 ] ] } ]

[ { "id": "PMID-1568251_T1", "type": "Protein", "text": [ "Histone H4" ], "offsets": [ [ 0, 10 ] ], "normalized": [] }, { "id": "PMID-1568251_T2", "type": "Protein", "text": [ "Histone H4" ], "offsets": [ [ 143, 153 ] ], "normalized": [] }, { "id": "PMID-1568251_T3", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 380, 382 ] ], "normalized": [] }, { "id": "PMID-1568251_T4", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 623, 625 ] ], "normalized": [] }, { "id": "PMID-1568251_T5", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 651, 653 ] ], "normalized": [] }, { "id": "PMID-1568251_T6", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 878, 880 ] ], "normalized": [] }, { "id": "PMID-1568251_T8", "type": "Entity", "text": [ "lysine" ], "offsets": [ [ 43, 49 ] ], "normalized": [] }, { "id": "PMID-1568251_T10", "type": "Entity", "text": [ "lysines 5" ], "offsets": [ [ 177, 186 ] ], "normalized": [] }, { "id": "PMID-1568251_T11", "type": "Entity", "text": [ "8" ], "offsets": [ [ 188, 189 ] ], "normalized": [] }, { "id": "PMID-1568251_T12", "type": "Entity", "text": [ "12" ], "offsets": [ [ 191, 193 ] ], "normalized": [] }, { "id": "PMID-1568251_T13", "type": "Entity", "text": [ "16" ], "offsets": [ [ 198, 200 ] ], "normalized": [] }, { "id": "PMID-1568251_T15", "type": "Entity", "text": [ "lysines 5" ], "offsets": [ [ 407, 416 ] ], "normalized": [] }, { "id": "PMID-1568251_T16", "type": "Entity", "text": [ "8" ], "offsets": [ [ 420, 421 ] ], "normalized": [] }, { "id": "PMID-1568251_T18", "type": "Entity", "text": [ "lysine 12" ], "offsets": [ [ 640, 649 ] ], "normalized": [] }, { "id": "PMID-1568251_T20", "type": "Entity", "text": [ "lysine 16" ], "offsets": [ [ 668, 677 ] ], "normalized": [] } ]

[ { "id": "PMID-1568251_E1", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 20, 30 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1568251_T1" }, { "role": "Site", "ref_id": "PMID-1568251_T8" } ] }, { "id": "PMID-1568251_E2", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 163, 173 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1568251_T2" }, { "role": "Site", "ref_id": "PMID-1568251_T10" } ] }, { "id": "PMID-1568251_E3", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 163, 173 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1568251_T2" }, { "role": "Site", "ref_id": "PMID-1568251_T11" } ] }, { "id": "PMID-1568251_E4", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 163, 173 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1568251_T2" }, { "role": "Site", "ref_id": "PMID-1568251_T12" } ] }, { "id": "PMID-1568251_E5", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 163, 173 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1568251_T2" }, { "role": "Site", "ref_id": "PMID-1568251_T13" } ] }, { "id": "PMID-1568251_E6", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 393, 403 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1568251_T3" }, { "role": "Site", "ref_id": "PMID-1568251_T15" } ] }, { "id": "PMID-1568251_E7", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 393, 403 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1568251_T3" }, { "role": "Site", "ref_id": "PMID-1568251_T16" } ] }, { "id": "PMID-1568251_E8", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 626, 636 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1568251_T4" }, { "role": "Site", "ref_id": "PMID-1568251_T18" } ] }, { "id": "PMID-1568251_E9", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 654, 664 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1568251_T5" }, { "role": "Site", "ref_id": "PMID-1568251_T20" } ] }, { "id": "PMID-1568251_E10", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 891, 901 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1568251_T6" } ] } ]

[]

[]

[ { "id": "PMID-15691383__text", "type": "abstract", "text": [ "The loss of NKX3.1 expression in testicular--and prostate--cancers is not caused by promoter hypermethylation. \nBACKGROUND: Recent studies have demonstrated that the NKX3.1 protein is commonly down-regulated in testicular germ cell tumors (TGCTs) and prostate carcinomas. The homeobox gene NKX3.1 maps to chromosome band 8p21, which is a region frequently lost in prostate cancer, but not in TGCT. Mutations have not been reported in the NKX3.1 sequence, and the gene is hypothesized to be epigenetically inactivated. In the present study we examined the methylation status of the NKX3.1 promoter in relevant primary tumors and cell lines: primary TGCTs (n = 55), intratubular germ cell neoplasias (n = 7), germ cell tumor cell lines (n = 3), primary prostate adenocarcinomas (n = 20), and prostate cancer cell lines (n = 3) by methylation-specific PCR and bisulphite sequencing. RESULTS AND CONCLUSIONS: Down-regulation of NKX3.1 expression was generally not caused by promoter hypermethylation, which was only found in one TGCT. However, other epigenetic mechanisms, such as modulation of chromatin structure or modifications of histones, may explain the lack of NKX3.1 expression, which is seen in most TGCTs and prostate cancer specimens.\n" ], "offsets": [ [ 0, 1243 ] ] } ]

[ { "id": "PMID-15691383_T1", "type": "Protein", "text": [ "NKX3.1" ], "offsets": [ [ 12, 18 ] ], "normalized": [] }, { "id": "PMID-15691383_T2", "type": "Protein", "text": [ "NKX3.1" ], "offsets": [ [ 166, 172 ] ], "normalized": [] }, { "id": "PMID-15691383_T3", "type": "Protein", "text": [ "NKX3.1" ], "offsets": [ [ 290, 296 ] ], "normalized": [] }, { "id": "PMID-15691383_T4", "type": "Protein", "text": [ "NKX3.1" ], "offsets": [ [ 438, 444 ] ], "normalized": [] }, { "id": "PMID-15691383_T5", "type": "Protein", "text": [ "NKX3.1" ], "offsets": [ [ 581, 587 ] ], "normalized": [] }, { "id": "PMID-15691383_T6", "type": "Protein", "text": [ "NKX3.1" ], "offsets": [ [ 924, 930 ] ], "normalized": [] }, { "id": "PMID-15691383_T7", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 1131, 1139 ] ], "normalized": [] }, { "id": "PMID-15691383_T8", "type": "Protein", "text": [ "NKX3.1" ], "offsets": [ [ 1165, 1171 ] ], "normalized": [] }, { "id": "PMID-15691383_T9", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 84, 92 ] ], "normalized": [] }, { "id": "PMID-15691383_T12", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 588, 596 ] ], "normalized": [] }, { "id": "PMID-15691383_T13", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 970, 978 ] ], "normalized": [] } ]

[ { "id": "PMID-15691383_E1", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylation" ], "offsets": [ [ 93, 109 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15691383_T1" }, { "role": "Site", "ref_id": "PMID-15691383_T9" } ] }, { "id": "PMID-15691383_E2", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 555, 566 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15691383_T5" }, { "role": "Site", "ref_id": "PMID-15691383_T12" } ] }, { "id": "PMID-15691383_E3", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylation" ], "offsets": [ [ 979, 995 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15691383_T6" }, { "role": "Site", "ref_id": "PMID-15691383_T13" } ] } ]

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[ { "id": "PMID-15691768__text", "type": "abstract", "text": [ "Bre1 is required for Notch signaling and histone modification. \nNotch signaling controls numerous cell fate decisions during animal development. These typically involve a Notch-mediated switch in transcription of target genes, although the details of this molecular mechanism are poorly understood. Here, we identify dBre1 as a nuclear component required cell autonomously for the expression of Notch target genes in Drosophila development. dBre1 affects the levels of Su(H) in imaginal disc cells, and it stimulates the Su(H)-mediated transcription of a Notch-specific reporter in transfected Drosophila cells. Strikingly, dBre1 mutant clones show much reduced levels of methylated lysine 4 on histone 3 (H3K4m), a chromatin mark that has been implicated in transcriptional activation. Thus, dBre1 is the functional homolog of yeast Bre1p, an E3 ubiquitin ligase required for the monoubiquitination of histone H2B and, indirectly, for H3K4 methylation. Our results indicate that histone modification is critical for the transcription of Notch target genes.\n" ], "offsets": [ [ 0, 1058 ] ] } ]

[ { "id": "PMID-15691768_T1", "type": "Protein", "text": [ "Bre1" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-15691768_T2", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 41, 48 ] ], "normalized": [] }, { "id": "PMID-15691768_T3", "type": "Protein", "text": [ "dBre1" ], "offsets": [ [ 317, 322 ] ], "normalized": [] }, { "id": "PMID-15691768_T4", "type": "Protein", "text": [ "dBre1" ], "offsets": [ [ 441, 446 ] ], "normalized": [] }, { "id": "PMID-15691768_T5", "type": "Protein", "text": [ "Su(H)" ], "offsets": [ [ 469, 474 ] ], "normalized": [] }, { "id": "PMID-15691768_T6", "type": "Protein", "text": [ "Su(H)" ], "offsets": [ [ 521, 526 ] ], "normalized": [] }, { "id": "PMID-15691768_T7", "type": "Protein", "text": [ "dBre1" ], "offsets": [ [ 624, 629 ] ], "normalized": [] }, { "id": "PMID-15691768_T8", "type": "Protein", "text": [ "histone 3" ], "offsets": [ [ 695, 704 ] ], "normalized": [] }, { "id": "PMID-15691768_T9", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 706, 708 ] ], "normalized": [] }, { "id": "PMID-15691768_T10", "type": "Protein", "text": [ "dBre1" ], "offsets": [ [ 793, 798 ] ], "normalized": [] }, { "id": "PMID-15691768_T11", "type": "Protein", "text": [ "Bre1p" ], "offsets": [ [ 834, 839 ] ], "normalized": [] }, { "id": "PMID-15691768_T12", "type": "Protein", "text": [ "histone H2B" ], "offsets": [ [ 903, 914 ] ], "normalized": [] }, { "id": "PMID-15691768_T13", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 936, 938 ] ], "normalized": [] }, { "id": "PMID-15691768_T14", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 980, 987 ] ], "normalized": [] }, { "id": "PMID-15691768_T16", "type": "Entity", "text": [ "lysine 4" ], "offsets": [ [ 683, 691 ] ], "normalized": [] }, { "id": "PMID-15691768_T17", "type": "Entity", "text": [ "K4" ], "offsets": [ [ 708, 710 ] ], "normalized": [] }, { "id": "PMID-15691768_T20", "type": "Entity", "text": [ "K4" ], "offsets": [ [ 938, 940 ] ], "normalized": [] } ]

[ { "id": "PMID-15691768_E1", "type": "Methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 672, 682 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15691768_T8" }, { "role": "Site", "ref_id": "PMID-15691768_T16" } ] }, { "id": "PMID-15691768_E2", "type": "Catalysis", "trigger": { "text": [ "required for" ], "offsets": [ [ 864, 876 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15691768_E3" }, { "role": "Cause", "ref_id": "PMID-15691768_T11" } ] }, { "id": "PMID-15691768_E3", "type": "Ubiquitination", "trigger": { "text": [ "monoubiquitination" ], "offsets": [ [ 881, 899 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15691768_T12" } ] }, { "id": "PMID-15691768_E4", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 941, 952 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15691768_T13" }, { "role": "Site", "ref_id": "PMID-15691768_T20" } ] } ]

[ { "id": "PMID-15691768_1", "entity_ids": [ "PMID-15691768_T16", "PMID-15691768_T17" ] }, { "id": "PMID-15691768_2", "entity_ids": [ "PMID-15691768_T8", "PMID-15691768_T9" ] } ]

[]

[ { "id": "PMID-15698950__text", "type": "abstract", "text": [ "Identification and characterization of novel endogenous proteolytic forms of the human angiogenesis inhibitors restin and endostatin. \nRestin and endostatin are C-terminal fragments of the noncollagenous domains of collagen XV and collagen XVIII exhibiting high sequence homology. Both polypeptides are distinguished by strong anti-angiogenic activity in vivo restricting the growth of solid tumors and metastasis. They are therefore currently being tested in clinical trials as anti-cancer drugs. We present the identification of new endogenous variants of both angiogenesis inhibitors isolated from a human hemofiltrate peptide library. Using an immunological screening approach with time-resolved rare earth metal fluorometry, immunoreactive compounds were purified chromatographically and characterized by mass spectrometry. We discovered four novel proteolytic products of restin as well as four variants of endostatin. Two endostatin products were characterized as short internal fragments (R176-L215 and R176-S219) of the entire molecule containing the recently identified beta1 integrin receptor binding site, which plays a major role in endothelial cell migration and angiogenesis. Two additional forms contain mucin-type O-glycosylations. The O-glycosylated variants possess an oligosaccharide unit consisting of one N-acetylgalactosamine (GalNAc), one N-acetylneuraminic acid (NANA) and two galactose residues (Gal) occurring as sialo-(V117-S311-GalNAc-Gal2-NANA) and asialoglycopeptides (V117-S311-GalNAc-Gal2). The four restin variants (R(I)-R(IV)) were identified with identical C- but different N-termini and no posttranslational modification (R(I): P66-A254, R(II): P75-A254, R(III): Y81-A254 and R(IV): A89-A254). Following a differential peptide mass fingerprint approach by reflector mode MALDI-TOFMS, the disulfide patterns of these circulating restins were determined as Cys1-Cys4 and Cys2-Cys3. These endogenous circulating collagen fragments will help to understand the physiological processing of the therapeutic proteins.\n" ], "offsets": [ [ 0, 2047 ] ] } ]

[ { "id": "PMID-15698950_T1", "type": "Protein", "text": [ "restin" ], "offsets": [ [ 111, 117 ] ], "normalized": [] }, { "id": "PMID-15698950_T2", "type": "Protein", "text": [ "endostatin" ], "offsets": [ [ 122, 132 ] ], "normalized": [] }, { "id": "PMID-15698950_T3", "type": "Protein", "text": [ "Restin" ], "offsets": [ [ 135, 141 ] ], "normalized": [] }, { "id": "PMID-15698950_T4", "type": "Protein", "text": [ "endostatin" ], "offsets": [ [ 146, 156 ] ], "normalized": [] }, { "id": "PMID-15698950_T5", "type": "Protein", "text": [ "collagen XV" ], "offsets": [ [ 215, 226 ] ], "normalized": [] }, { "id": "PMID-15698950_T6", "type": "Protein", "text": [ "collagen XVIII" ], "offsets": [ [ 231, 245 ] ], "normalized": [] }, { "id": "PMID-15698950_T7", "type": "Protein", "text": [ "restin" ], "offsets": [ [ 878, 884 ] ], "normalized": [] }, { "id": "PMID-15698950_T8", "type": "Protein", "text": [ "endostatin" ], "offsets": [ [ 913, 923 ] ], "normalized": [] }, { "id": "PMID-15698950_T9", "type": "Protein", "text": [ "endostatin" ], "offsets": [ [ 929, 939 ] ], "normalized": [] }, { "id": "PMID-15698950_T10", "type": "Protein", "text": [ "beta1 integrin" ], "offsets": [ [ 1080, 1094 ] ], "normalized": [] }, { "id": "PMID-15698950_T11", "type": "Protein", "text": [ "restin" ], "offsets": [ [ 1533, 1539 ] ], "normalized": [] }, { "id": "PMID-15698950_T12", "type": "Protein", "text": [ "restins" ], "offsets": [ [ 1865, 1872 ] ], "normalized": [] }, { "id": "PMID-15698950_T15", "type": "Entity", "text": [ "S311" ], "offsets": [ [ 1452, 1456 ] ], "normalized": [] }, { "id": "PMID-15698950_T16", "type": "Entity", "text": [ "GalNAc-Gal2-NANA" ], "offsets": [ [ 1457, 1473 ] ], "normalized": [] }, { "id": "PMID-15698950_T17", "type": "Entity", "text": [ "S311" ], "offsets": [ [ 1505, 1509 ] ], "normalized": [] }, { "id": "PMID-15698950_T18", "type": "Entity", "text": [ "GalNAc-Gal2" ], "offsets": [ [ 1510, 1521 ] ], "normalized": [] } ]

[ { "id": "PMID-15698950_E1", "type": "Glycosylation", "trigger": { "text": [ "O-glycosylations" ], "offsets": [ [ 1231, 1247 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15698950_T9" } ] }, { "id": "PMID-15698950_E2", "type": "Glycosylation", "trigger": { "text": [ "O-glycosylated" ], "offsets": [ [ 1253, 1267 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15698950_T9" }, { "role": "Site", "ref_id": "PMID-15698950_T15" }, { "role": "Sidechain", "ref_id": "PMID-15698950_T16" } ] }, { "id": "PMID-15698950_E3", "type": "Glycosylation", "trigger": { "text": [ "O-glycosylated" ], "offsets": [ [ 1253, 1267 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15698950_T9" }, { "role": "Site", "ref_id": "PMID-15698950_T17" }, { "role": "Sidechain", "ref_id": "PMID-15698950_T18" } ] } ]

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[ { "id": "PMID-15735726__text", "type": "abstract", "text": [ "Analysis of methylation-sensitive transcriptome identifies GADD45a as a frequently methylated gene in breast cancer. \nTreatment of the breast cancer cell line, MDAMB468 with the DNA methylation inhibitor, 5-azacytidine (5-AzaC) results in growth arrest, whereas the growth of the normal breast epithelial line DU99 (telomerase immortalized) is relatively unaffected. Comparing gene expression profiles of these two lines after 5-AzaC treatment, we identified 36 genes that had relatively low basal levels in MDAMB468 cells compared to the DU99 line and were induced in the cancer cell line but not in the normal breast epithelial line. Of these genes, 33 have associated CpG islands greater than 300 bp in length but only three have been previously described as targets for aberrant methylation in human cancer. Northern blotting for five of these genes (alpha-Catenin, DTR, FYN, GADD45a, and Zyxin) verified the array results. Further analysis of one of these genes, GADD45a, showed that 5-AzaC induced expression in five additional breast cancer cell lines with little or no induction in three additional lines derived from normal breast epithelial cells. The CpG island associated with GADD45a was analysed by bisulfite sequencing, sampling over 100 CpG dinucleotides. We found that four CpG's, located approximately 700 bp upstream of the transcriptional start site are methylated in the majority of breast cancer cell lines and primary tumors but not in DNA from normal breast epithelia or matched lymphocytes from cancer patients. Therefore, this simple method of dynamic transcriptional profiling yielded a series of novel methylation-sensitive genes in breast cancer including the BRCA1 and p53 responsive gene, GADD45a.\n" ], "offsets": [ [ 0, 1729 ] ] } ]

[ { "id": "PMID-15735726_T1", "type": "Protein", "text": [ "GADD45a" ], "offsets": [ [ 59, 66 ] ], "normalized": [] }, { "id": "PMID-15735726_T2", "type": "Protein", "text": [ "alpha-Catenin" ], "offsets": [ [ 855, 868 ] ], "normalized": [] }, { "id": "PMID-15735726_T3", "type": "Protein", "text": [ "DTR" ], "offsets": [ [ 870, 873 ] ], "normalized": [] }, { "id": "PMID-15735726_T4", "type": "Protein", "text": [ "FYN" ], "offsets": [ [ 875, 878 ] ], "normalized": [] }, { "id": "PMID-15735726_T5", "type": "Protein", "text": [ "GADD45a" ], "offsets": [ [ 880, 887 ] ], "normalized": [] }, { "id": "PMID-15735726_T6", "type": "Protein", "text": [ "Zyxin" ], "offsets": [ [ 893, 898 ] ], "normalized": [] }, { "id": "PMID-15735726_T7", "type": "Protein", "text": [ "GADD45a" ], "offsets": [ [ 968, 975 ] ], "normalized": [] }, { "id": "PMID-15735726_T8", "type": "Protein", "text": [ "GADD45a" ], "offsets": [ [ 1189, 1196 ] ], "normalized": [] }, { "id": "PMID-15735726_T9", "type": "Protein", "text": [ "BRCA1" ], "offsets": [ [ 1689, 1694 ] ], "normalized": [] }, { "id": "PMID-15735726_T10", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 1699, 1702 ] ], "normalized": [] }, { "id": "PMID-15735726_T11", "type": "Protein", "text": [ "GADD45a" ], "offsets": [ [ 1720, 1727 ] ], "normalized": [] }, { "id": "PMID-15735726_T13", "type": "Entity", "text": [ "four CpG" ], "offsets": [ [ 1286, 1294 ] ], "normalized": [] } ]

[ { "id": "PMID-15735726_E1", "type": "DNA_methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 83, 93 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15735726_T1" } ] }, { "id": "PMID-15735726_E2", "type": "DNA_methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 1374, 1384 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15735726_T8" }, { "role": "Site", "ref_id": "PMID-15735726_T13" } ] }, { "id": "PMID-15735726_E3", "type": "DNA_methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 1374, 1384 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15735726_T8" }, { "role": "Site", "ref_id": "PMID-15735726_T13" } ] } ]

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[ { "id": "PMID-15753298__text", "type": "abstract", "text": [ "Osteocalcin protein sequences of Neanderthals and modern primates. \nWe report here protein sequences of fossil hominids, from two Neanderthals dating to approximately 75,000 years old from Shanidar Cave in Iraq. These sequences, the oldest reported fossil primate protein sequences, are of bone osteocalcin, which was extracted and sequenced by using MALDI-TOF/TOF mass spectrometry. Through a combination of direct sequencing and peptide mass mapping, we determined that Neanderthals have an osteocalcin amino acid sequence that is identical to that of modern humans. We also report complete osteocalcin sequences for chimpanzee (Pan troglodytes) and gorilla (Gorilla gorilla gorilla) and a partial sequence for orangutan (Pongo pygmaeus), all of which are previously unreported. We found that the osteocalcin sequences of Neanderthals, modern human, chimpanzee, and orangutan are unusual among mammals in that the ninth amino acid is proline (Pro-9), whereas most species have hydroxyproline (Hyp-9). Posttranslational hydroxylation of Pro-9 in osteocalcin by prolyl-4-hydroxylase requires adequate concentrations of vitamin C (l-ascorbic acid), molecular O(2), Fe(2+), and 2-oxoglutarate, and also depends on enzyme recognition of the target proline substrate consensus sequence Leu-Gly-Ala-Pro-9-Ala-Pro-Tyr occurring in most mammals. In five species with Pro-9-Val-10, hydroxylation is blocked, whereas in gorilla there is a mixture of Pro-9 and Hyp-9. We suggest that the absence of hydroxylation of Pro-9 in Pan, Pongo, and Homo may reflect response to a selective pressure related to a decline in vitamin C in the diet during omnivorous dietary adaptation, either independently or through the common ancestor of these species.\n" ], "offsets": [ [ 0, 1735 ] ] } ]

[ { "id": "PMID-15753298_T1", "type": "Protein", "text": [ "Osteocalcin" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "PMID-15753298_T2", "type": "Protein", "text": [ "osteocalcin" ], "offsets": [ [ 295, 306 ] ], "normalized": [] }, { "id": "PMID-15753298_T3", "type": "Protein", "text": [ "osteocalcin" ], "offsets": [ [ 493, 504 ] ], "normalized": [] }, { "id": "PMID-15753298_T4", "type": "Protein", "text": [ "osteocalcin" ], "offsets": [ [ 593, 604 ] ], "normalized": [] }, { "id": "PMID-15753298_T5", "type": "Protein", "text": [ "osteocalcin" ], "offsets": [ [ 799, 810 ] ], "normalized": [] }, { "id": "PMID-15753298_T6", "type": "Protein", "text": [ "osteocalcin" ], "offsets": [ [ 1047, 1058 ] ], "normalized": [] }, { "id": "PMID-15753298_T8", "type": "Entity", "text": [ "Pro-9" ], "offsets": [ [ 1038, 1043 ] ], "normalized": [] }, { "id": "PMID-15753298_T11", "type": "Entity", "text": [ "Pro-9" ], "offsets": [ [ 1506, 1511 ] ], "normalized": [] } ]

[ { "id": "PMID-15753298_E1", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 1021, 1034 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15753298_T6" }, { "role": "Site", "ref_id": "PMID-15753298_T8" } ] }, { "id": "PMID-15753298_E2", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 1374, 1387 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15753298_T6" } ] }, { "id": "PMID-15753298_E3", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 1489, 1502 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15753298_T6" }, { "role": "Site", "ref_id": "PMID-15753298_T11" } ] } ]

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[]

[ { "id": "PMID-15767660__text", "type": "abstract", "text": [ "Relationship between histone H3 lysine 9 methylation, transcription repression, and heterochromatin protein 1 recruitment. \nHistone H3 lysine 9 (H3-K9) methylation has been shown to correlate with transcriptional repression and serve as a specific binding site for heterochromatin protein 1 (HP1). In this study, we investigated the relationship between H3-K9 methylation, transcriptional repression, and HP1 recruitment by comparing the effects of tethering two H3-K9-specific histone methyltransferases, SUV39H1 and G9a, to chromatin on transcription and HP1 recruitment. Although both SUV39H1 and G9a induced H3-K9 methylation and repressed transcription, only SUV39H1 was able to recruit HP1 to chromatin. Targeting HP1 to chromatin required not only K9 methylation but also a direct protein-protein interaction between SUV39H1 and HP1. Targeting methyl-K9 or a HP1-interacting region of SUV39H1 alone to chromatin was not sufficient to recruit HP1. We also demonstrate that methyl-K9 can suppress transcription independently of HP1 through a mechanism involving histone deacetylation. In an effort to understand how H3-K9 methylation led to histone deacetylation in both H3 and H4, we found that H3-K9 methylation inhibited histone acetylation by p300 but not its association with chromatin. Collectively, these data indicate that H3-K9 methylation alone can suppress transcription but is insufficient for HP1 recruitment in the context of chromatin exemplifying the importance of chromatin-associated factors in reading the histone code.\n" ], "offsets": [ [ 0, 1544 ] ] } ]

[ { "id": "PMID-15767660_T1", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 21, 31 ] ], "normalized": [] }, { "id": "PMID-15767660_T2", "type": "Protein", "text": [ "Histone H3" ], "offsets": [ [ 124, 134 ] ], "normalized": [] }, { "id": "PMID-15767660_T3", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 145, 147 ] ], "normalized": [] }, { "id": "PMID-15767660_T4", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 354, 356 ] ], "normalized": [] }, { "id": "PMID-15767660_T5", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 463, 465 ] ], "normalized": [] }, { "id": "PMID-15767660_T6", "type": "Protein", "text": [ "SUV39H1" ], "offsets": [ [ 506, 513 ] ], "normalized": [] }, { "id": "PMID-15767660_T7", "type": "Protein", "text": [ "G9a" ], "offsets": [ [ 518, 521 ] ], "normalized": [] }, { "id": "PMID-15767660_T8", "type": "Protein", "text": [ "SUV39H1" ], "offsets": [ [ 588, 595 ] ], "normalized": [] }, { "id": "PMID-15767660_T9", "type": "Protein", "text": [ "G9a" ], "offsets": [ [ 600, 603 ] ], "normalized": [] }, { "id": "PMID-15767660_T10", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 612, 614 ] ], "normalized": [] }, { "id": "PMID-15767660_T11", "type": "Protein", "text": [ "SUV39H1" ], "offsets": [ [ 664, 671 ] ], "normalized": [] }, { "id": "PMID-15767660_T12", "type": "Protein", "text": [ "SUV39H1" ], "offsets": [ [ 824, 831 ] ], "normalized": [] }, { "id": "PMID-15767660_T13", "type": "Protein", "text": [ "SUV39H1" ], "offsets": [ [ 892, 899 ] ], "normalized": [] }, { "id": "PMID-15767660_T14", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1067, 1074 ] ], "normalized": [] }, { "id": "PMID-15767660_T15", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1121, 1123 ] ], "normalized": [] }, { "id": "PMID-15767660_T16", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1146, 1153 ] ], "normalized": [] }, { "id": "PMID-15767660_T17", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1176, 1178 ] ], "normalized": [] }, { "id": "PMID-15767660_T18", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 1183, 1185 ] ], "normalized": [] }, { "id": "PMID-15767660_T19", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1201, 1203 ] ], "normalized": [] }, { "id": "PMID-15767660_T20", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1229, 1236 ] ], "normalized": [] }, { "id": "PMID-15767660_T21", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 1252, 1256 ] ], "normalized": [] }, { "id": "PMID-15767660_T22", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1336, 1338 ] ], "normalized": [] }, { "id": "PMID-15767660_T23", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1530, 1537 ] ], "normalized": [] }, { "id": "PMID-15767660_T24", "type": "Entity", "text": [ "lysine 9" ], "offsets": [ [ 32, 40 ] ], "normalized": [] }, { "id": "PMID-15767660_T26", "type": "Entity", "text": [ "lysine 9" ], "offsets": [ [ 135, 143 ] ], "normalized": [] }, { "id": "PMID-15767660_T27", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 148, 150 ] ], "normalized": [] }, { "id": "PMID-15767660_T29", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 357, 359 ] ], "normalized": [] }, { "id": "PMID-15767660_T32", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 615, 617 ] ], "normalized": [] }, { "id": "PMID-15767660_T34", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 755, 757 ] ], "normalized": [] }, { "id": "PMID-15767660_T37", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 1204, 1206 ] ], "normalized": [] }, { "id": "PMID-15767660_T41", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 1339, 1341 ] ], "normalized": [] } ]

[ { "id": "PMID-15767660_E1", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 41, 52 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15767660_T1" }, { "role": "Site", "ref_id": "PMID-15767660_T24" } ] }, { "id": "PMID-15767660_E2", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 152, 163 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15767660_T2" }, { "role": "Site", "ref_id": "PMID-15767660_T26" } ] }, { "id": "PMID-15767660_E3", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 360, 371 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15767660_T4" }, { "role": "Site", "ref_id": "PMID-15767660_T29" } ] }, { "id": "PMID-15767660_E4", "type": "Catalysis", "trigger": { "text": [ "induced" ], "offsets": [ [ 604, 611 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15767660_E6" }, { "role": "Cause", "ref_id": "PMID-15767660_T8" } ] }, { "id": "PMID-15767660_E5", "type": "Catalysis", "trigger": { "text": [ "induced" ], "offsets": [ [ 604, 611 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15767660_E6" }, { "role": "Cause", "ref_id": "PMID-15767660_T9" } ] }, { "id": "PMID-15767660_E6", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 618, 629 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15767660_T10" }, { "role": "Site", "ref_id": "PMID-15767660_T32" } ] }, { "id": "PMID-15767660_E7", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 758, 769 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15767660_T10" }, { "role": "Site", "ref_id": "PMID-15767660_T34" } ] }, { "id": "PMID-15767660_E8", "type": "Deacetylation", "trigger": { "text": [ "deacetylation" ], "offsets": [ [ 1075, 1088 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15767660_T14" } ] }, { "id": "PMID-15767660_E9", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1207, 1218 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15767660_T19" }, { "role": "Site", "ref_id": "PMID-15767660_T37" } ] }, { "id": "PMID-15767660_E10", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 1237, 1248 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15767660_T20" } ] }, { "id": "PMID-15767660_E11", "type": "Catalysis", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 1237, 1248 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15767660_E10" }, { "role": "Cause", "ref_id": "PMID-15767660_T21" } ] }, { "id": "PMID-15767660_E12", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1342, 1353 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15767660_T22" }, { "role": "Site", "ref_id": "PMID-15767660_T41" } ] } ]

[ { "id": "PMID-15767660_1", "entity_ids": [ "PMID-15767660_T2", "PMID-15767660_T3" ] }, { "id": "PMID-15767660_2", "entity_ids": [ "PMID-15767660_T26", "PMID-15767660_T27" ] } ]

[]

[ { "id": "PMID-15804608__text", "type": "abstract", "text": [ "A simple, sensitive in vitro assay for cytoplasmic deglycosylation by peptide: N-glycanase. \nA cytoplasmic peptide: N-glycanase (PNGase) has been implicated in the proteasomal degradation of aberrant glycoproteins synthesized in the endoplasmic reticulum. The reaction is believed to be important for subsequent proteolysis by the proteasome since bulky N-glycan chains on misfolded glycoproteins may impair their efficient entry into the interior of the cylinder-shaped 20S proteasome, where its active site resides. This cytoplasmic enzyme was first detected in 1993 by a simple, sensitive assay method using 14C-labeled glycopeptide as a substrate. The deglycosylation reaction by PNGase brings about two major changes on substrate the peptide; one is removal of the N-glycan chain and the other is the introduction of a negative charge into the core peptide by converting the glycosylated asparagine residue(s) into an aspartic acid residue(s). The assay method we developed monitors these major changes in the core peptide, and the respective changes were detected by distinct analytical methods: i.e., paper chromatography and paper electrophoresis. This chapter will describe the simple, sensitive in vitro assay method for PNGase.\n" ], "offsets": [ [ 0, 1239 ] ] } ]

[ { "id": "PMID-15804608_T1", "type": "Protein", "text": [ "peptide: N-glycanase" ], "offsets": [ [ 70, 90 ] ], "normalized": [] }, { "id": "PMID-15804608_T2", "type": "Protein", "text": [ "peptide: N-glycanase" ], "offsets": [ [ 107, 127 ] ], "normalized": [] }, { "id": "PMID-15804608_T3", "type": "Protein", "text": [ "PNGase" ], "offsets": [ [ 129, 135 ] ], "normalized": [] }, { "id": "PMID-15804608_T4", "type": "Protein", "text": [ "PNGase" ], "offsets": [ [ 684, 690 ] ], "normalized": [] }, { "id": "PMID-15804608_T5", "type": "Protein", "text": [ "PNGase" ], "offsets": [ [ 1231, 1237 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-15804608_1", "entity_ids": [ "PMID-15804608_T2", "PMID-15804608_T3" ] } ]

[]

[ { "id": "PMID-15823564__text", "type": "abstract", "text": [ "In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells. \nIn addition to long-term self-renewal capability, human mesenchymal stem cells (MSCs) possess versatile differentiation potential ranging from mesenchyme-related multipotency to neuroectodermal and endodermal competency. Of particular concern is hepatogenic potential that can be used for liver-directed stem cell therapy and transplantation. In this study, we have investigated whether human umbilical cord blood (UCB)-derived MSCs are also able to differentiate into hepatocyte-like cells. MSCs isolated from UCB were cultured under the pro-hepatogenic condition similar to that for bone marrow (BM)-derived MSCs. Expression of a variety of hepatic lineage markers was analyzed by flow cytometry, RT-PCR, Western blot, and immunofluorescence. The functionality of differentiated cells was assessed by their ability to incorporate DiI-acetylated low-density lipoprotein (DiI-Ac-LDL). As the cells were morphologically transformed into hepatocyte-like cells, they expressed Thy-1, c-Kit, and Flt-3 at the cell surface, as well as albumin, alpha-fetoprotein, and cytokeratin-18 and 19 in the interior. Moreover, about a half of the cells were found to acquire the capability to transport DiI-Ac-LDL. Based on these observations, and taking into account immense advantages of UCB over other stem cell sources, we conclude that UCB-derived MSCs retain hepatogenic potential suitable for cell therapy and transplantation against intractable liver diseases.\n" ], "offsets": [ [ 0, 1568 ] ] } ]

[ { "id": "PMID-15823564_T1", "type": "Protein", "text": [ "Thy-1" ], "offsets": [ [ 1089, 1094 ] ], "normalized": [] }, { "id": "PMID-15823564_T2", "type": "Protein", "text": [ "c-Kit" ], "offsets": [ [ 1096, 1101 ] ], "normalized": [] }, { "id": "PMID-15823564_T3", "type": "Protein", "text": [ "Flt-3" ], "offsets": [ [ 1107, 1112 ] ], "normalized": [] }, { "id": "PMID-15823564_T4", "type": "Protein", "text": [ "albumin" ], "offsets": [ [ 1145, 1152 ] ], "normalized": [] }, { "id": "PMID-15823564_T5", "type": "Protein", "text": [ "alpha-fetoprotein" ], "offsets": [ [ 1154, 1171 ] ], "normalized": [] }, { "id": "PMID-15823564_T6", "type": "Protein", "text": [ "cytokeratin-18" ], "offsets": [ [ 1177, 1191 ] ], "normalized": [] }, { "id": "PMID-15823564_T7", "type": "Protein", "text": [ "19" ], "offsets": [ [ 1196, 1198 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-15831483__text", "type": "abstract", "text": [ "Small interfering RNAs that trigger posttranscriptional gene silencing are not required for the histone H3 Lys9 methylation necessary for transgenic tandem repeat stabilization in Neurospora crassa. \nIn Neurospora crassa, the introduction of a transgene can lead to small interfering RNA (siRNA)-mediated posttranscriptional gene silencing (PTGS) of homologous genes. siRNAs can also guide locus-specific methylation of Lys9 of histone H3 (Lys9H3) in Schizosaccharomyces pombe. Here we tested the hypothesis that transgenically derived siRNAs may contemporaneously both activate the PTGS mechanism and induce chromatin modifications at the transgene and the homologous endogenous gene. We carried out chromatin immunoprecipitation using a previously characterized albino-1 (al-1) silenced strain but detected no alterations in the pattern of histone modifications at the endogenous al-1 locus, suggesting that siRNAs produced from the transgenic locus do not trigger modifications in trans of those histones tested. Instead, we found that the transgenic locus was hypermethylated at Lys9H3 in our silenced strain and remained hypermethylated in the quelling defective mutants (qde), further demonstrating that the PTGS machinery is dispensable for Lys9H3 methylation. However, we found that a mutant in the histone Lys9H3 methyltransferase dim-5 was unable to maintain PTGS, with transgenic copies being rapidly lost, resulting in reversion of the silenced phenotype. These results indicate that the defect in PTGS of the Deltadim-5 strain is due to the inability to maintain the transgene in tandem, suggesting a role for DIM-5 in stabilizing such repeated sequences. We conclude that in Neurospora, siRNAs produced from the transgenic locus are used in the RNA-induced silencing complex-mediated PTGS pathway and do not communicate with an RNAi-induced initiation of transcriptional gene silencing complex to effect chromatin-based silencing.\n" ], "offsets": [ [ 0, 1945 ] ] } ]

[ { "id": "PMID-15831483_T1", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 96, 106 ] ], "normalized": [] }, { "id": "PMID-15831483_T2", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 428, 438 ] ], "normalized": [] }, { "id": "PMID-15831483_T3", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 444, 446 ] ], "normalized": [] }, { "id": "PMID-15831483_T4", "type": "Protein", "text": [ "albino-1" ], "offsets": [ [ 764, 772 ] ], "normalized": [] }, { "id": "PMID-15831483_T5", "type": "Protein", "text": [ "al-1" ], "offsets": [ [ 774, 778 ] ], "normalized": [] }, { "id": "PMID-15831483_T6", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 842, 849 ] ], "normalized": [] }, { "id": "PMID-15831483_T7", "type": "Protein", "text": [ "al-1" ], "offsets": [ [ 882, 886 ] ], "normalized": [] }, { "id": "PMID-15831483_T8", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 999, 1007 ] ], "normalized": [] }, { "id": "PMID-15831483_T9", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1087, 1089 ] ], "normalized": [] }, { "id": "PMID-15831483_T10", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1252, 1254 ] ], "normalized": [] }, { "id": "PMID-15831483_T11", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1307, 1314 ] ], "normalized": [] }, { "id": "PMID-15831483_T12", "type": "Protein", "text": [ "dim-5" ], "offsets": [ [ 1340, 1345 ] ], "normalized": [] }, { "id": "PMID-15831483_T13", "type": "Protein", "text": [ "dim-5" ], "offsets": [ [ 1527, 1532 ] ], "normalized": [] }, { "id": "PMID-15831483_T14", "type": "Protein", "text": [ "DIM-5" ], "offsets": [ [ 1623, 1628 ] ], "normalized": [] }, { "id": "PMID-15831483_T15", "type": "Entity", "text": [ "Lys9" ], "offsets": [ [ 107, 111 ] ], "normalized": [] }, { "id": "PMID-15831483_T18", "type": "Entity", "text": [ "Lys9" ], "offsets": [ [ 420, 424 ] ], "normalized": [] }, { "id": "PMID-15831483_T19", "type": "Entity", "text": [ "Lys9" ], "offsets": [ [ 440, 444 ] ], "normalized": [] }, { "id": "PMID-15831483_T21", "type": "Entity", "text": [ "Lys9" ], "offsets": [ [ 1083, 1087 ] ], "normalized": [] }, { "id": "PMID-15831483_T23", "type": "Entity", "text": [ "Lys9" ], "offsets": [ [ 1248, 1252 ] ], "normalized": [] } ]

[ { "id": "PMID-15831483_E1", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 112, 123 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15831483_T1" }, { "role": "Site", "ref_id": "PMID-15831483_T15" } ] }, { "id": "PMID-15831483_E2", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 405, 416 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15831483_T2" }, { "role": "Site", "ref_id": "PMID-15831483_T18" } ] }, { "id": "PMID-15831483_E3", "type": "Methylation", "trigger": { "text": [ "hypermethylated" ], "offsets": [ [ 1064, 1079 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15831483_T9" }, { "role": "Site", "ref_id": "PMID-15831483_T21" }, { "role": "Contextgene", "ref_id": "PMID-15831483_T7" } ] }, { "id": "PMID-15831483_E4", "type": "Methylation", "trigger": { "text": [ "hypermethylated" ], "offsets": [ [ 1126, 1141 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15831483_T9" }, { "role": "Site", "ref_id": "PMID-15831483_T21" }, { "role": "Contextgene", "ref_id": "PMID-15831483_T7" } ] }, { "id": "PMID-15831483_E5", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1255, 1266 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15831483_T10" }, { "role": "Site", "ref_id": "PMID-15831483_T23" }, { "role": "Contextgene", "ref_id": "PMID-15831483_T7" } ] } ]

[ { "id": "PMID-15831483_1", "entity_ids": [ "PMID-15831483_T18", "PMID-15831483_T19" ] }, { "id": "PMID-15831483_2", "entity_ids": [ "PMID-15831483_T2", "PMID-15831483_T3" ] }, { "id": "PMID-15831483_3", "entity_ids": [ "PMID-15831483_T4", "PMID-15831483_T5" ] } ]

[]

[ { "id": "PMID-15833424__text", "type": "abstract", "text": [ "A rapid PCR method for genotyping the Large(myd) mouse, a model of glycosylation-deficient congenital muscular dystrophy. \nThe myodystrophy (Large(myd)) mouse has a spontaneous loss of function mutation in a putative glycosyltransferase gene (Large). Mutations in the human gene (LARGE) have been described in congenital muscular dystrophy type 1D (MDC1D). Mutations in four other genes that encode known or putative glycosylation enzymes (POMT1, POMGnT1, fukutin and FKRP) are also associated with muscular dystrophy. In all these diseases hypoglycosylation of alpha-dystroglycan, and consequent loss of ligand binding, is a common pathomechanism. Currently, the Large(myd) mouse is the principal animal model for studying the underlying molecular mechanisms of this group of disorders. Over-expression of LARGE in cells from patients with mutations in POMT1 or POMGnT1 results in hyperglycosylation of alpha-dystroglycan and restoration of laminin binding. Thus, LARGE is a potential therapeutic target. Here, we define the intronic deletion breakpoints of the Large(myd) mutation and describe a simple, PCR-based diagnostic assay, facilitating the study of this important animal model.\n" ], "offsets": [ [ 0, 1189 ] ] } ]

[ { "id": "PMID-15833424_T1", "type": "Protein", "text": [ "Large" ], "offsets": [ [ 141, 146 ] ], "normalized": [] }, { "id": "PMID-15833424_T2", "type": "Protein", "text": [ "LARGE" ], "offsets": [ [ 280, 285 ] ], "normalized": [] }, { "id": "PMID-15833424_T3", "type": "Protein", "text": [ "POMT1" ], "offsets": [ [ 440, 445 ] ], "normalized": [] }, { "id": "PMID-15833424_T4", "type": "Protein", "text": [ "POMGnT1" ], "offsets": [ [ 447, 454 ] ], "normalized": [] }, { "id": "PMID-15833424_T5", "type": "Protein", "text": [ "fukutin" ], "offsets": [ [ 456, 463 ] ], "normalized": [] }, { "id": "PMID-15833424_T6", "type": "Protein", "text": [ "FKRP" ], "offsets": [ [ 468, 472 ] ], "normalized": [] }, { "id": "PMID-15833424_T7", "type": "Protein", "text": [ "alpha-dystroglycan" ], "offsets": [ [ 562, 580 ] ], "normalized": [] }, { "id": "PMID-15833424_T8", "type": "Protein", "text": [ "Large" ], "offsets": [ [ 664, 669 ] ], "normalized": [] }, { "id": "PMID-15833424_T9", "type": "Protein", "text": [ "LARGE" ], "offsets": [ [ 807, 812 ] ], "normalized": [] }, { "id": "PMID-15833424_T10", "type": "Protein", "text": [ "POMT1" ], "offsets": [ [ 854, 859 ] ], "normalized": [] }, { "id": "PMID-15833424_T11", "type": "Protein", "text": [ "POMGnT1" ], "offsets": [ [ 863, 870 ] ], "normalized": [] }, { "id": "PMID-15833424_T12", "type": "Protein", "text": [ "alpha-dystroglycan" ], "offsets": [ [ 904, 922 ] ], "normalized": [] }, { "id": "PMID-15833424_T13", "type": "Protein", "text": [ "LARGE" ], "offsets": [ [ 965, 970 ] ], "normalized": [] }, { "id": "PMID-15833424_T14", "type": "Protein", "text": [ "Large" ], "offsets": [ [ 1063, 1068 ] ], "normalized": [] } ]

[ { "id": "PMID-15833424_E1", "type": "Glycosylation", "trigger": { "text": [ "hypoglycosylation" ], "offsets": [ [ 541, 558 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15833424_T7" } ] }, { "id": "PMID-15833424_E2", "type": "Glycosylation", "trigger": { "text": [ "hyperglycosylation" ], "offsets": [ [ 882, 900 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15833424_T12" } ] } ]

[]

[]

[ { "id": "PMID-15908192__text", "type": "abstract", "text": [ "Minoxidil exerts different inhibitory effects on gene expression of lysyl hydroxylase 1, 2, and 3: implications for collagen cross-linking and treatment of fibrosis. \nCollagen deposits in fibrotic lesions often display elevated levels of hydroxyallysine (pyridinoline) cross-links. The relation between the occurrence of pyridinoline cross-links and the irreversibility of fibrosis suggests that these cross-links contribute to the aberrant accumulation of collagen. Based on its inhibitory effect on lysyl hydroxylase activity minoxidil has been postulated to possess anti-fibrotic properties by limiting the hydroxylysine supply for hydroxyallysine cross-linking. However, to interfere with hydroxyallysine cross-linking specifically lysyl hydroxylation of the collagen telopeptide should be inhibited, a reaction predominantly catalysed by lysyl hydroxylase (LH) 2b. In this study, we demonstrate that minoxidil treatment of cultured fibroblasts reduces LH1>>LH2b>LH3 mRNA levels dose-and time-dependently, but has essentially no effect on the total number of pyridinoline cross-links in the collagen matrix. Still the collagen produced in the presence of minoxidil displays some remarkable features: hydroxylation of triple helical lysine residues is reduced to 50% and lysylpyridinoline cross-linking is increased at the expense of hydroxylysylpyridinoline cross-linking. These observations can be explained by our finding that LH1 mRNA levels are the most sensitive to minoxidil treatment, corroborating that LH1 has a preference for triple helical lysine residues as substrate. In addition, the non-proportional increase in cross-links (20-fold) with respect to the decrease in lysyl hydroxylation state of the triple helix (2-fold) even suggests that LH1 preferentially hydroxylates triple helical lysine residues at the cross-link positions. We conclude that minoxidil is unlikely to serve as an anti-fibroticum, but confers features to the collagen matrix, which provide insight into the substrate specificity of LH1.\n" ], "offsets": [ [ 0, 2028 ] ] } ]

[ { "id": "PMID-15908192_T1", "type": "Protein", "text": [ "lysyl hydroxylase 1" ], "offsets": [ [ 68, 87 ] ], "normalized": [] }, { "id": "PMID-15908192_T2", "type": "Protein", "text": [ "2" ], "offsets": [ [ 89, 90 ] ], "normalized": [] }, { "id": "PMID-15908192_T3", "type": "Protein", "text": [ "3" ], "offsets": [ [ 96, 97 ] ], "normalized": [] }, { "id": "PMID-15908192_T4", "type": "Protein", "text": [ "lysyl hydroxylase (LH) 2b" ], "offsets": [ [ 843, 868 ] ], "normalized": [] }, { "id": "PMID-15908192_T5", "type": "Protein", "text": [ "LH1" ], "offsets": [ [ 957, 960 ] ], "normalized": [] }, { "id": "PMID-15908192_T6", "type": "Protein", "text": [ "LH2b" ], "offsets": [ [ 962, 966 ] ], "normalized": [] }, { "id": "PMID-15908192_T7", "type": "Protein", "text": [ "LH3" ], "offsets": [ [ 967, 970 ] ], "normalized": [] }, { "id": "PMID-15908192_T8", "type": "Protein", "text": [ "LH1" ], "offsets": [ [ 1433, 1436 ] ], "normalized": [] }, { "id": "PMID-15908192_T9", "type": "Protein", "text": [ "LH1" ], "offsets": [ [ 1515, 1518 ] ], "normalized": [] }, { "id": "PMID-15908192_T10", "type": "Protein", "text": [ "LH1" ], "offsets": [ [ 1759, 1762 ] ], "normalized": [] }, { "id": "PMID-15908192_T11", "type": "Protein", "text": [ "LH1" ], "offsets": [ [ 2023, 2026 ] ], "normalized": [] } ]

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[ { "id": "PMID-1590827__text", "type": "abstract", "text": [ "Association of N-glycosylation of apolipoprotein B-100 with plasma cholesterol levels in Watanabe heritable hyperlipidemic rabbits. \nWe have previously demonstrated the heterogeneity of N-linked sugar chains of apolipoprotein (apo) B-100 in Watanabe heritable hyperlipidemic (WHHL) rabbit and fasting Japanese White rabbits (Arteriosclerosis, 10 (1990) 386-393). To investigate further the role of N-linked sugar chains of apo B-100 in lipid metabolism, we examined the correlation between the N-glycosylation of apo B-100 and serum cholesterol levels in WHHL rabbits. The N-linked sugar chains of apo B-100 were liberated by hydrazinolysis, followed by NaB3H4 reduction and were fractionated by paper electrophoresis and BioGel P-4 column chromatography. These were found to consist of one neutral (N) and two acidic fractions (A1 and A2). N contained a high mannose type oligosaccharide consisting of Man5.GlcNAc2 to Man9.GlcNAc2, while A1 and A2 contained monosialylated and disialylated complex type oligosaccharides, respectively. The molar ratio varied among the 5 WHHL rabbits. There was an inverse correlation between the ratio of acidic oligosaccharide fractions (A1 + A2) and serum cholesterol levels (r = -0.971, P less than 0.01) in the 5 WHHL rabbits. These results indicate that the N-glycosylation of apo B-100 is closely related to cholesterol metabolism in WHHL rabbits.\n" ], "offsets": [ [ 0, 1388 ] ] } ]

[ { "id": "PMID-1590827_T1", "type": "Protein", "text": [ "apolipoprotein B-100" ], "offsets": [ [ 34, 54 ] ], "normalized": [] }, { "id": "PMID-1590827_T2", "type": "Protein", "text": [ "apolipoprotein (apo) B-100" ], "offsets": [ [ 211, 237 ] ], "normalized": [] }, { "id": "PMID-1590827_T3", "type": "Protein", "text": [ "apo B-100" ], "offsets": [ [ 423, 432 ] ], "normalized": [] }, { "id": "PMID-1590827_T4", "type": "Protein", "text": [ "apo B-100" ], "offsets": [ [ 513, 522 ] ], "normalized": [] }, { "id": "PMID-1590827_T5", "type": "Protein", "text": [ "apo B-100" ], "offsets": [ [ 598, 607 ] ], "normalized": [] }, { "id": "PMID-1590827_T6", "type": "Protein", "text": [ "apo B-100" ], "offsets": [ [ 1316, 1325 ] ], "normalized": [] }, { "id": "PMID-1590827_T9", "type": "Entity", "text": [ "sugar chains" ], "offsets": [ [ 195, 207 ] ], "normalized": [] }, { "id": "PMID-1590827_T11", "type": "Entity", "text": [ "sugar chains" ], "offsets": [ [ 407, 419 ] ], "normalized": [] }, { "id": "PMID-1590827_T14", "type": "Entity", "text": [ "sugar chains" ], "offsets": [ [ 582, 594 ] ], "normalized": [] } ]

[ { "id": "PMID-1590827_E1", "type": "Glycosylation", "trigger": { "text": [ "N-glycosylation" ], "offsets": [ [ 15, 30 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1590827_T1" } ] }, { "id": "PMID-1590827_E2", "type": "Glycosylation", "trigger": { "text": [ "N-linked" ], "offsets": [ [ 186, 194 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1590827_T2" }, { "role": "Sidechain", "ref_id": "PMID-1590827_T9" } ] }, { "id": "PMID-1590827_E3", "type": "Glycosylation", "trigger": { "text": [ "N-linked" ], "offsets": [ [ 398, 406 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1590827_T3" }, { "role": "Sidechain", "ref_id": "PMID-1590827_T11" } ] }, { "id": "PMID-1590827_E4", "type": "Glycosylation", "trigger": { "text": [ "N-glycosylation" ], "offsets": [ [ 494, 509 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1590827_T4" } ] }, { "id": "PMID-1590827_E5", "type": "Glycosylation", "trigger": { "text": [ "N-linked" ], "offsets": [ [ 573, 581 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1590827_T5" }, { "role": "Sidechain", "ref_id": "PMID-1590827_T14" } ] }, { "id": "PMID-1590827_E6", "type": "Glycosylation", "trigger": { "text": [ "N-glycosylation" ], "offsets": [ [ 1297, 1312 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1590827_T6" } ] } ]

[]

[]

[ { "id": "PMID-15912425__text", "type": "abstract", "text": [ "Two C-methyl derivatives of [11C]WAY-100635--effects of an amido alpha-methyl group on metabolism and brain 5-HT1A receptor radioligand behavior in monkey. \nPURPOSE: [carbonyl-11C]N-(2-(1-(4-(2-methoxyphenyl)-piperazinyl)ethyl)-N-pyridinyl)cyclohexanecarboxamide ([carbonyl-11C]WAY-100635) is an effective radioligand for imaging brain 5-HT1A receptors with positron emission tomography (PET). However, this radioligand has some drawbacks for deriving relative regional receptor densities, including rapid metabolism, which acts against accurate definition of an arterial input function for compartmental modeling, and very low nonspecific binding in brain, which detracts from the accuracy of modeling by a simplified reference tissue (cerebellum) approach. Here, in a search for a radioligand that overcomes these limitations, we investigated the effects of introducing a single methyl group at either of the carbon atoms alpha to the amide bond in [11C]WAY-100635. PROCEDURES: Ligands with a methyl group on the alpha carbon of the cyclohexyl group (SWAY) or the alpha carbon of the C2H4 linker ((R,S)-JWAY) were synthesized and tested for binding affinity and intrinsic activity at 5-HT1A receptors. SWAY was labeled with carbon-11 (t1/2 = 20.4 minutes; beta+ = 99.8%) in its O-methyl group and (R,S)-JWAY in its carbonyl group. Each radioligand was evaluated by PET experiments in cynomolgus monkey. RESULTS: SWAY and (R,S)-JWAY were found to be high-affinity antagonists at 5-HT1A receptors. After injection of [11C]SWAY into monkey, radioactivity uptake in brain reached a maximum of 3% at 4.5 minutes and decreased to 0.7% at 72 minutes. However, over the time span of the experiment, radioactivity concentrations in 5-HT1A receptor-rich brain regions were only fractionally higher than in cerebellum. Radioactivity represented by parent radioligand in plasma was 39% at 45 minutes. After injection of [11C](R,S)-JWAY alone, radioactivity uptake in brain reached a maximum of 4.8% at 2.5 minutes and decreased to 1.2% at 90 minutes. At this time, radioactivity concentration in 5-HT1A receptor-rich brain regions was markedly greater than in cerebellum. In another PET experiment, the monkey was predosed with WAY-100635 before [11C](R,S)-JWAY injection. At 90 minutes after injection, the ratio of radioactivity in 5-HT1A receptor-rich regions to that in cerebellum was reduced to near unity. Radioactivity represented by parent radioligand in plasma was 12% at 45 minutes. CONCLUSIONS: [11C](R,S)-JWAY, but not [11C]SWAY, gives a sizeable 5-HT1A receptor-selective PET signal in monkey. The presence of a C-methyl group adjacent to the amide bond in SWAY or (R,S)-JWAY fails to counter metabolism.\n" ], "offsets": [ [ 0, 2708 ] ] } ]

[ { "id": "PMID-15912425_T1", "type": "Protein", "text": [ "5-HT1A" ], "offsets": [ [ 108, 114 ] ], "normalized": [] }, { "id": "PMID-15912425_T2", "type": "Protein", "text": [ "5-HT1A" ], "offsets": [ [ 336, 342 ] ], "normalized": [] }, { "id": "PMID-15912425_T3", "type": "Protein", "text": [ "5-HT1A" ], "offsets": [ [ 1186, 1192 ] ], "normalized": [] }, { "id": "PMID-15912425_T4", "type": "Protein", "text": [ "5-HT1A" ], "offsets": [ [ 1480, 1486 ] ], "normalized": [] }, { "id": "PMID-15912425_T5", "type": "Protein", "text": [ "5-HT1A" ], "offsets": [ [ 1725, 1731 ] ], "normalized": [] }, { "id": "PMID-15912425_T6", "type": "Protein", "text": [ "5-HT1A" ], "offsets": [ [ 2086, 2092 ] ], "normalized": [] }, { "id": "PMID-15912425_T7", "type": "Protein", "text": [ "5-HT1A" ], "offsets": [ [ 2324, 2330 ] ], "normalized": [] }, { "id": "PMID-15912425_T8", "type": "Protein", "text": [ "5-HT1A" ], "offsets": [ [ 2549, 2555 ] ], "normalized": [] } ]

[]

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[]

[ { "id": "PMID-15919754__text", "type": "abstract", "text": [ "Effects of histone acetylation on sodium iodide symporter promoter and expression of thyroid-specific transcription factors. \nInhibitors of histone deacetylases (HDACs) activate the sodium iodide symporter (NIS) expression in thyroid tumor cells. In this study, mechanisms accounting for these effects were investigated. Various human thyroid tumor cell lines (ARO, BCPAP, FRO, TPC-1) were treated with the HDAC inhibitors Na butyrate (NaB) and tricostatin A (TSA), and the effects on the expression of NIS and several thyroid-specific transcription factors together with the activity of NIS promoter were evaluated. TSA and NaB increased NIS mRNA levels in all cell lines. Among thyroid-specific transcription factors, only expression of PAX8 in ARO cells was increased. Down-regulation of thyroid-specific transcription factor-1 expression was observed in BCPAP and TPC-1 cell lines. Thyroid-specific transcription factor-2 mRNA was reduced in FRO, BCPAP, and TPC-1 cells. Histone acetylation had no significant effects on HEX expression. Altogether, these data indicate that the increase of NIS expression is not mediated by modification of expression of thyroid-specific transcription factors. Accordingly, in transfection experiments performed in the HeLa cell line (which does not express thyroid-specific transcription factors), treatment with TSA and NaB increased NIS promoter activity. Stimulation of NIS promoter activity was also obtained by overexpressing histone acetylating proteins pCAF and p300 in HeLa cells. Conversely, overexpression of the HDAC 1 enzyme inhibited basal activity of the NIS promoter. Effects of TSA and NaB on NIS expression were also evaluated in nonthyroid cell lines MCF-7, Hep-G2, and SAOS-2. In all cell lines TSA and NaB greatly increased NIS mRNA levels. We concluded that control of NIS expression by inhibition of HDAC appears not to be mediated by cell-specific mechanisms, suggesting it as a potential strategy to induce radioiodine sensitivity in different human tumors.\n" ], "offsets": [ [ 0, 2020 ] ] } ]

[ { "id": "PMID-15919754_T1", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 11, 18 ] ], "normalized": [] }, { "id": "PMID-15919754_T2", "type": "Protein", "text": [ "sodium iodide symporter" ], "offsets": [ [ 34, 57 ] ], "normalized": [] }, { "id": "PMID-15919754_T3", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 140, 147 ] ], "normalized": [] }, { "id": "PMID-15919754_T4", "type": "Protein", "text": [ "sodium iodide symporter" ], "offsets": [ [ 182, 205 ] ], "normalized": [] }, { "id": "PMID-15919754_T5", "type": "Protein", "text": [ "NIS" ], "offsets": [ [ 207, 210 ] ], "normalized": [] }, { "id": "PMID-15919754_T6", "type": "Protein", "text": [ "NIS" ], "offsets": [ [ 503, 506 ] ], "normalized": [] }, { "id": "PMID-15919754_T7", "type": "Protein", "text": [ "NIS" ], "offsets": [ [ 588, 591 ] ], "normalized": [] }, { "id": "PMID-15919754_T8", "type": "Protein", "text": [ "NIS" ], "offsets": [ [ 639, 642 ] ], "normalized": [] }, { "id": "PMID-15919754_T9", "type": "Protein", "text": [ "PAX8" ], "offsets": [ [ 739, 743 ] ], "normalized": [] }, { "id": "PMID-15919754_T10", "type": "Protein", "text": [ "thyroid-specific transcription factor-1" ], "offsets": [ [ 791, 830 ] ], "normalized": [] }, { "id": "PMID-15919754_T11", "type": "Protein", "text": [ "Thyroid-specific transcription factor-2" ], "offsets": [ [ 886, 925 ] ], "normalized": [] }, { "id": "PMID-15919754_T12", "type": "Protein", "text": [ "Histone" ], "offsets": [ [ 975, 982 ] ], "normalized": [] }, { "id": "PMID-15919754_T13", "type": "Protein", "text": [ "HEX" ], "offsets": [ [ 1025, 1028 ] ], "normalized": [] }, { "id": "PMID-15919754_T14", "type": "Protein", "text": [ "NIS" ], "offsets": [ [ 1094, 1097 ] ], "normalized": [] }, { "id": "PMID-15919754_T15", "type": "Protein", "text": [ "NIS" ], "offsets": [ [ 1373, 1376 ] ], "normalized": [] }, { "id": "PMID-15919754_T16", "type": "Protein", "text": [ "NIS" ], "offsets": [ [ 1411, 1414 ] ], "normalized": [] }, { "id": "PMID-15919754_T17", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1469, 1476 ] ], "normalized": [] }, { "id": "PMID-15919754_T18", "type": "Protein", "text": [ "pCAF" ], "offsets": [ [ 1498, 1502 ] ], "normalized": [] }, { "id": "PMID-15919754_T19", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 1507, 1511 ] ], "normalized": [] }, { "id": "PMID-15919754_T20", "type": "Protein", "text": [ "HDAC 1" ], "offsets": [ [ 1561, 1567 ] ], "normalized": [] }, { "id": "PMID-15919754_T21", "type": "Protein", "text": [ "NIS" ], "offsets": [ [ 1607, 1610 ] ], "normalized": [] }, { "id": "PMID-15919754_T22", "type": "Protein", "text": [ "NIS" ], "offsets": [ [ 1647, 1650 ] ], "normalized": [] }, { "id": "PMID-15919754_T23", "type": "Protein", "text": [ "NIS" ], "offsets": [ [ 1782, 1785 ] ], "normalized": [] }, { "id": "PMID-15919754_T24", "type": "Protein", "text": [ "NIS" ], "offsets": [ [ 1828, 1831 ] ], "normalized": [] } ]

[ { "id": "PMID-15919754_E1", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 19, 30 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15919754_T1" }, { "role": "Contextgene", "ref_id": "PMID-15919754_T2" } ] }, { "id": "PMID-15919754_E2", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 983, 994 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15919754_T12" } ] } ]

[ { "id": "PMID-15919754_1", "entity_ids": [ "PMID-15919754_T4", "PMID-15919754_T5" ] } ]

[]

[ { "id": "PMID-15969742__text", "type": "abstract", "text": [ "Astrocyte- and hepatocyte-specific expression of genes from the distal serpin subcluster at 14q32.1 associates with tissue-specific chromatin structures. \nThe distal serpin subcluster contains genes encoding alpha1-antichymotrypsin (ACT), protein C inhibitor (PCI), kallistatin (KAL) and the KAL-like protein, which are expressed in hepatocytes, but only the act gene is expressed in astrocytes. We show here that the tissue-specific expression of these genes associates with astrocyte- and hepatocyte-specific chromatin structures. In hepatocytes, we identified 12 Dnase I-hypersensitive sites (DHSs) that were distributed throughout the entire subcluster, with the promoters of expressed genes accessible to restriction enzyme digestion. In astrocytes, only six DHSs were located exclusively in the 5' flanking region of the act gene, with its promoter also accessible to restriction enzyme digestion. The acetylation of histone H3 and H4 was found throughout the subcluster in both cell types but this acetylation did not correlate with the expression pattern of these serpin genes. Analysis of histone modifications at the promoters of the act and pci genes revealed that methylation of histone H3 on lysine 4 correlated with their expression pattern in both cell types. In addition, inhibition of methyltransferase activity resulted in suppression of ACT and PCI mRNA expression. We propose that lysine 4 methylation of histone H3 correlates with the tissue-specific expression pattern of these serpin genes.\n" ], "offsets": [ [ 0, 1514 ] ] } ]

[ { "id": "PMID-15969742_T1", "type": "Protein", "text": [ "alpha1-antichymotrypsin" ], "offsets": [ [ 208, 231 ] ], "normalized": [] }, { "id": "PMID-15969742_T2", "type": "Protein", "text": [ "ACT" ], "offsets": [ [ 233, 236 ] ], "normalized": [] }, { "id": "PMID-15969742_T3", "type": "Protein", "text": [ "protein C inhibitor" ], "offsets": [ [ 239, 258 ] ], "normalized": [] }, { "id": "PMID-15969742_T4", "type": "Protein", "text": [ "PCI" ], "offsets": [ [ 260, 263 ] ], "normalized": [] }, { "id": "PMID-15969742_T5", "type": "Protein", "text": [ "kallistatin" ], "offsets": [ [ 266, 277 ] ], "normalized": [] }, { "id": "PMID-15969742_T6", "type": "Protein", "text": [ "KAL" ], "offsets": [ [ 279, 282 ] ], "normalized": [] }, { "id": "PMID-15969742_T7", "type": "Protein", "text": [ "act" ], "offsets": [ [ 359, 362 ] ], "normalized": [] }, { "id": "PMID-15969742_T8", "type": "Protein", "text": [ "Dnase I" ], "offsets": [ [ 566, 573 ] ], "normalized": [] }, { "id": "PMID-15969742_T9", "type": "Protein", "text": [ "act" ], "offsets": [ [ 827, 830 ] ], "normalized": [] }, { "id": "PMID-15969742_T10", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 923, 933 ] ], "normalized": [] }, { "id": "PMID-15969742_T11", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 938, 940 ] ], "normalized": [] }, { "id": "PMID-15969742_T12", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1098, 1105 ] ], "normalized": [] }, { "id": "PMID-15969742_T13", "type": "Protein", "text": [ "act" ], "offsets": [ [ 1144, 1147 ] ], "normalized": [] }, { "id": "PMID-15969742_T14", "type": "Protein", "text": [ "pci" ], "offsets": [ [ 1152, 1155 ] ], "normalized": [] }, { "id": "PMID-15969742_T15", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 1191, 1201 ] ], "normalized": [] }, { "id": "PMID-15969742_T16", "type": "Protein", "text": [ "ACT" ], "offsets": [ [ 1356, 1359 ] ], "normalized": [] }, { "id": "PMID-15969742_T17", "type": "Protein", "text": [ "PCI" ], "offsets": [ [ 1364, 1367 ] ], "normalized": [] }, { "id": "PMID-15969742_T18", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 1425, 1435 ] ], "normalized": [] }, { "id": "PMID-15969742_T21", "type": "Entity", "text": [ "lysine 4" ], "offsets": [ [ 1205, 1213 ] ], "normalized": [] }, { "id": "PMID-15969742_T22", "type": "Entity", "text": [ "lysine 4" ], "offsets": [ [ 1401, 1409 ] ], "normalized": [] } ]

[ { "id": "PMID-15969742_E1", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 908, 919 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15969742_T10" }, { "role": "Contextgene", "ref_id": "PMID-15969742_T9" } ] }, { "id": "PMID-15969742_E2", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 908, 919 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15969742_T11" }, { "role": "Contextgene", "ref_id": "PMID-15969742_T9" } ] }, { "id": "PMID-15969742_E3", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1176, 1187 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15969742_T15" }, { "role": "Site", "ref_id": "PMID-15969742_T21" }, { "role": "Contextgene", "ref_id": "PMID-15969742_T13" } ] }, { "id": "PMID-15969742_E4", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1176, 1187 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15969742_T15" }, { "role": "Site", "ref_id": "PMID-15969742_T21" }, { "role": "Contextgene", "ref_id": "PMID-15969742_T14" } ] }, { "id": "PMID-15969742_E5", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1410, 1421 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15969742_T18" }, { "role": "Site", "ref_id": "PMID-15969742_T22" }, { "role": "Contextgene", "ref_id": "PMID-15969742_T16" } ] }, { "id": "PMID-15969742_E6", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1410, 1421 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15969742_T18" }, { "role": "Site", "ref_id": "PMID-15969742_T22" }, { "role": "Contextgene", "ref_id": "PMID-15969742_T17" } ] } ]

[ { "id": "PMID-15969742_1", "entity_ids": [ "PMID-15969742_T1", "PMID-15969742_T2" ] }, { "id": "PMID-15969742_2", "entity_ids": [ "PMID-15969742_T3", "PMID-15969742_T4" ] }, { "id": "PMID-15969742_3", "entity_ids": [ "PMID-15969742_T5", "PMID-15969742_T6" ] } ]

[]

[ { "id": "PMID-15972824__text", "type": "abstract", "text": [ "Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity. \nDuox2 (and probably Duox1) is a glycoflavoprotein involved in thyroid hormone biosynthesis, as the thyroid H2O2 generator functionally associated with Tpo (thyroperoxidase). So far, because of the impairment of maturation and of the targeting process, transfecting DUOX into nonthyroid cell lines has not led to the expression of a functional H2O2-generating system at the plasma membrane. For the first time, we investigated the H2O2-generating activity in the particulate fractions from DUOX2- and DUOX1-transfected HEK293 and Chinese hamster ovary cells. The particulate fractions of these cells stably or transiently transfected with human or porcine DUOX cDNA demonstrate a functional NADPH/Ca2+-dependent H2O2-generating activity. The immature Duox proteins had less activity than pig thyrocyte particulate fractions, and their activity depended on their primary structures. Human Duox2 seemed to be more active than human Duox1 but only half as active as its porcine counterpart. TPO co-transfection produced a slight increase in the enzymatic activity, whereas p22(phox), the 22-kDa subunit of the leukocyte NADPH oxidase, had no effect. In previous studies on the mechanism of H2O2 formation, it was shown that mature thyroid NADPH oxidase does not release O2*- but H2O2. Using a spin-trapping technique combined with electron paramagnetic resonance spectroscopy, we confirmed this result but also demonstrated that the partially glycosylated form of Duox2, located in the endoplasmic reticulum, generates superoxide in a calcium-dependent manner. These results suggest that post-translational modifications during the maturation process of Duox2 could be implicated in the mechanism of H2O2 formation by favoring intramolecular superoxide dismutation.\n" ], "offsets": [ [ 0, 1836 ] ] } ]

[ { "id": "PMID-15972824_T1", "type": "Protein", "text": [ "Dual oxidase-2" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "PMID-15972824_T2", "type": "Protein", "text": [ "Duox2" ], "offsets": [ [ 74, 79 ] ], "normalized": [] }, { "id": "PMID-15972824_T3", "type": "Protein", "text": [ "Duox1" ], "offsets": [ [ 94, 99 ] ], "normalized": [] }, { "id": "PMID-15972824_T4", "type": "Protein", "text": [ "Tpo" ], "offsets": [ [ 225, 228 ] ], "normalized": [] }, { "id": "PMID-15972824_T5", "type": "Protein", "text": [ "thyroperoxidase" ], "offsets": [ [ 230, 245 ] ], "normalized": [] }, { "id": "PMID-15972824_T6", "type": "Protein", "text": [ "DUOX2" ], "offsets": [ [ 563, 568 ] ], "normalized": [] }, { "id": "PMID-15972824_T7", "type": "Protein", "text": [ "DUOX1" ], "offsets": [ [ 574, 579 ] ], "normalized": [] }, { "id": "PMID-15972824_T8", "type": "Protein", "text": [ "Duox2" ], "offsets": [ [ 961, 966 ] ], "normalized": [] }, { "id": "PMID-15972824_T9", "type": "Protein", "text": [ "Duox1" ], "offsets": [ [ 1003, 1008 ] ], "normalized": [] }, { "id": "PMID-15972824_T10", "type": "Protein", "text": [ "TPO" ], "offsets": [ [ 1061, 1064 ] ], "normalized": [] }, { "id": "PMID-15972824_T11", "type": "Protein", "text": [ "p22(phox)" ], "offsets": [ [ 1143, 1152 ] ], "normalized": [] }, { "id": "PMID-15972824_T12", "type": "Protein", "text": [ "Duox2" ], "offsets": [ [ 1534, 1539 ] ], "normalized": [] }, { "id": "PMID-15972824_T13", "type": "Protein", "text": [ "Duox2" ], "offsets": [ [ 1724, 1729 ] ], "normalized": [] } ]

[ { "id": "PMID-15972824_E1", "type": "Glycosylation", "trigger": { "text": [ "glycosylated" ], "offsets": [ [ 1513, 1525 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-15972824_T12" } ] } ]

[ { "id": "PMID-15972824_1", "entity_ids": [ "PMID-15972824_T4", "PMID-15972824_T5" ] } ]

[]

[ { "id": "PMID-15978544__text", "type": "abstract", "text": [ "The inactivation of bovine cathepsin B by novel N-chloro-acetyl-dipeptides: application of the Houghten 'tea bag' methodology to inhibitor synthesis. \nIn this study, a series of N-chloro-acetylated dipeptides were synthesised by the application of Houghten's methodology of multiple analog peptide syntheses (MAPS). The peptides, all of which contain a C-terminal free acid, were tested as inactivators of bovine cathepsin B, in an attempt at exploiting the known and, amongst the cysteine proteinases, unique carboxy dipeptidyl peptidase activity of the protease. We have succeeded in obtaining a number of effective inactivators, the most potent of which-chloroacetyl-Leu-Leu-OH, inactivates the enzyme with an apparent second-order rate constant of 3.8 x 10(4)M(-1)min(-1). In contrast, the esterified analog, chloroacetyl-Leu-Leu-OMe, inactivates the enzyme some three orders of magnitude less efficiently, lending credence to our thesis that a free carboxylic acid moiety is an important determinant for inhibitor effectiveness. This preliminary study has highlighted a number of interesting features about the specificity requirements of the bovine proteinase and we believe that our approach has great potential for the rapid delineation of the subsite specificities of cathepsin B-like proteases from various species.\n" ], "offsets": [ [ 0, 1326 ] ] } ]

[ { "id": "PMID-15978544_T1", "type": "Protein", "text": [ "cathepsin B" ], "offsets": [ [ 27, 38 ] ], "normalized": [] }, { "id": "PMID-15978544_T2", "type": "Protein", "text": [ "cathepsin B" ], "offsets": [ [ 413, 424 ] ], "normalized": [] }, { "id": "PMID-15978544_T3", "type": "Protein", "text": [ "cathepsin B" ], "offsets": [ [ 1277, 1288 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-16024066__text", "type": "abstract", "text": [ "Epigenetic-mediated upregulation of progesterone receptor B gene in endometrial cancer cell lines. \nOBJECTIVES: To determine if epigenetic interference can restore progesterone receptor-B (PR-B) expression in PR-B negative endometrial adenocarcinoma cell lines, and to characterize the kinetics of PR-B induction mediated by DNA methyltransferase and histone deacetylase inhibitors. METHODS: The PR-B negative endometrioid cancer cell lines KLE and HEC-1B were used as study models. PR-B mRNA and protein expression levels were measured using real-time PCR and Western blot analysis, respectively. DNA methylation levels of the PR-B promoter were determined by methylation-specific PCR. Dose-response correlations and the duration of response to aza-deoxycytidine (ADC) and trichostatin A (TSA) were characterized. Cell responses to prolonged and repeated drug treatment were also examined. RESULTS: Relatively low concentrations of ADC and TSA over a 24-h period induced PR-B expression. Furthermore, ADC and TSA acted synergistically to reactivate PR-B expression. Depending on the cell line used, PR-B mRNA was induced 10-110 fold. This elevated PR-B expression continued for 48 h after drug withdrawal. Sustained upregulation of PR-B mRNA and protein was observed during prolonged and repeated drug treatment. CONCLUSION: The epigenetically silenced PR-B gene remains sensitive to changes in DNA demethylation and histone acetylation in uterine adenocarcinoma cell lines. Treatment with ADC and/or TSA results in a robust and sustainable PR-B upregulation. These small molecule epigenetic modifying agents may be used to sensitize poorly differentiated, PR-B negative endometrial cancers to progestational therapy.\n" ], "offsets": [ [ 0, 1719 ] ] } ]

[ { "id": "PMID-16024066_T1", "type": "Protein", "text": [ "progesterone receptor B" ], "offsets": [ [ 36, 59 ] ], "normalized": [] }, { "id": "PMID-16024066_T2", "type": "Protein", "text": [ "progesterone receptor-B" ], "offsets": [ [ 164, 187 ] ], "normalized": [] }, { "id": "PMID-16024066_T3", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 189, 193 ] ], "normalized": [] }, { "id": "PMID-16024066_T4", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 209, 213 ] ], "normalized": [] }, { "id": "PMID-16024066_T5", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 298, 302 ] ], "normalized": [] }, { "id": "PMID-16024066_T6", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 351, 358 ] ], "normalized": [] }, { "id": "PMID-16024066_T7", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 396, 400 ] ], "normalized": [] }, { "id": "PMID-16024066_T8", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 483, 487 ] ], "normalized": [] }, { "id": "PMID-16024066_T9", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 628, 632 ] ], "normalized": [] }, { "id": "PMID-16024066_T10", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 972, 976 ] ], "normalized": [] }, { "id": "PMID-16024066_T11", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 1050, 1054 ] ], "normalized": [] }, { "id": "PMID-16024066_T12", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 1100, 1104 ] ], "normalized": [] }, { "id": "PMID-16024066_T13", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 1149, 1153 ] ], "normalized": [] }, { "id": "PMID-16024066_T14", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 1233, 1237 ] ], "normalized": [] }, { "id": "PMID-16024066_T15", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 1354, 1358 ] ], "normalized": [] }, { "id": "PMID-16024066_T16", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1418, 1425 ] ], "normalized": [] }, { "id": "PMID-16024066_T17", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 1542, 1546 ] ], "normalized": [] }, { "id": "PMID-16024066_T18", "type": "Protein", "text": [ "PR-B" ], "offsets": [ [ 1658, 1662 ] ], "normalized": [] }, { "id": "PMID-16024066_T20", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 633, 641 ] ], "normalized": [] } ]

[ { "id": "PMID-16024066_E1", "type": "DNA_methylation", "trigger": { "text": [ "DNA methylation" ], "offsets": [ [ 598, 613 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16024066_T9" }, { "role": "Site", "ref_id": "PMID-16024066_T20" } ] }, { "id": "PMID-16024066_E2", "type": "DNA_demethylation", "trigger": { "text": [ "DNA demethylation" ], "offsets": [ [ 1396, 1413 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16024066_T15" } ] }, { "id": "PMID-16024066_E3", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 1426, 1437 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16024066_T16" }, { "role": "Contextgene", "ref_id": "PMID-16024066_T15" } ] } ]

[ { "id": "PMID-16024066_1", "entity_ids": [ "PMID-16024066_T2", "PMID-16024066_T3" ] } ]

[]

[ { "id": "PMID-16037490__text", "type": "abstract", "text": [ "Differential analysis of site-specific glycans on plasma and cellular fibronectins: application of a hydrophilic affinity method for glycopeptide enrichment. \nIsolation of glycopeptides utilizing hydrogen bonding between glycopeptide glycans and a carbohydrate-gel matrix in the organic phase is useful for site-specific characterization of oligosaccharides of glycoproteins, when combined with mass spectrometry. In this study, recovery of glycopeptides was improved by including divalent cations or increasing the organic solvent in the binding solution, without losing specificity, whereas it was still less effective for those with a long peptide backbone exceeding 50 amino acid residues. The method was then applied to the analysis of glycan heterogeneities at seven N-glycosylation sites in each of the plasma and cellular fibronectins (FNs). There was a remarkable site-specific difference in fucosylation between these isoforms; Asn1244 selectively escaped the global fucosylation of cellular FN, whereas only Asn1007 and Asn2108 of the plasma isoform underwent modification. In addition, a new O-glycosylation site was identified at Thr279 in the connecting segment between the fibrin- and heparin-binding domain and the collagen-binding domain, and the glycopeptide was reactive to a peanut agglutinin lectin. Considering that another mucin-type O-glycosylation site lies within a different connecting segment, the O-glycosylation of FN was suggested to play a significant role in segregating the neighboring domains and thus maintaining the topology of FN and the domain functions. In addition, the method was applied to apolipoprotein B-100 (apoB100) whose N-glycan structures at 17 of 19 potential sites have been reported, and characterized the remaining sites. The results also demonstrated that the enriched glycopeptide provides resources for site-specific analysis of oligosaccharides in glycoproteomics.\n" ], "offsets": [ [ 0, 1924 ] ] } ]

[ { "id": "PMID-16037490_T1", "type": "Protein", "text": [ "fibronectins" ], "offsets": [ [ 70, 82 ] ], "normalized": [] }, { "id": "PMID-16037490_T2", "type": "Protein", "text": [ "fibronectins" ], "offsets": [ [ 830, 842 ] ], "normalized": [] }, { "id": "PMID-16037490_T3", "type": "Protein", "text": [ "FNs" ], "offsets": [ [ 844, 847 ] ], "normalized": [] }, { "id": "PMID-16037490_T4", "type": "Protein", "text": [ "FN" ], "offsets": [ [ 1002, 1004 ] ], "normalized": [] }, { "id": "PMID-16037490_T5", "type": "Protein", "text": [ "agglutinin" ], "offsets": [ [ 1302, 1312 ] ], "normalized": [] }, { "id": "PMID-16037490_T6", "type": "Protein", "text": [ "FN" ], "offsets": [ [ 1445, 1447 ] ], "normalized": [] }, { "id": "PMID-16037490_T7", "type": "Protein", "text": [ "FN" ], "offsets": [ [ 1565, 1567 ] ], "normalized": [] }, { "id": "PMID-16037490_T8", "type": "Protein", "text": [ "apolipoprotein B-100" ], "offsets": [ [ 1633, 1653 ] ], "normalized": [] }, { "id": "PMID-16037490_T9", "type": "Protein", "text": [ "apoB100" ], "offsets": [ [ 1655, 1662 ] ], "normalized": [] }, { "id": "PMID-16037490_T10", "type": "Entity", "text": [ "Asn1244" ], "offsets": [ [ 938, 945 ] ], "normalized": [] }, { "id": "PMID-16037490_T12", "type": "Entity", "text": [ "Asn1007" ], "offsets": [ [ 1019, 1026 ] ], "normalized": [] }, { "id": "PMID-16037490_T13", "type": "Entity", "text": [ "Asn2108" ], "offsets": [ [ 1031, 1038 ] ], "normalized": [] } ]

[ { "id": "PMID-16037490_E1", "type": "Glycosylation", "trigger": { "text": [ "fucosylation" ], "offsets": [ [ 977, 989 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16037490_T4" }, { "role": "Site", "ref_id": "PMID-16037490_T10" } ] }, { "id": "PMID-16037490_E2", "type": "Glycosylation", "trigger": { "text": [ "modification" ], "offsets": [ [ 1071, 1083 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16037490_T4" }, { "role": "Site", "ref_id": "PMID-16037490_T12" } ] }, { "id": "PMID-16037490_E3", "type": "Glycosylation", "trigger": { "text": [ "modification" ], "offsets": [ [ 1071, 1083 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16037490_T4" }, { "role": "Site", "ref_id": "PMID-16037490_T13" } ] }, { "id": "PMID-16037490_E4", "type": "Glycosylation", "trigger": { "text": [ "O-glycosylation" ], "offsets": [ [ 1426, 1441 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16037490_T6" } ] } ]

[ { "id": "PMID-16037490_1", "entity_ids": [ "PMID-16037490_T2", "PMID-16037490_T3" ] }, { "id": "PMID-16037490_2", "entity_ids": [ "PMID-16037490_T8", "PMID-16037490_T9" ] } ]

[]

[ { "id": "PMID-16082210__text", "type": "abstract", "text": [ "Histone acetylation, chromatin remodelling and nucleotide excision repair: hint from the study on MFA2 in Saccharomyces cerevisiae. \nNucleotide excision repair (NER) is a sophisticated repair pathway that the cell utilizes to remove a broad range of DNA damage to help maintain the functional integrity of the genome. In the context of DNA packaged into chromosomes it is clear that the NER machinery does not repair all regions with equal efficiency. Recently, we found after UV that histone acetylation and chromatin remodelling were activated. UV irradiation triggers genome-wide histone hyperacetylation at both histone H3 and H4. However, in nucleosomes at the repressed MFA2 promoter only histone H3, but not histone H4, is hyperacetylated following UV. This Gcn5p-mediated histone H3 hyperacetylation enables efficient NER at MFA2. Chromatin in this promoter also becomes more accessible after UV. This is not dependent on Gcn5p, yet it is partially dependent on Swi2p. In later repair times both events gradually return to the pre-UV state. The post-UV histone modifications and chromatin remodelling at the repressed MFA2 promoter do not activate MFA2 transcription, nor do they require damage recognition by Rad4p or Rad14p. These experiments indicate early events are triggered in chromatin in response to UV treatment, and they are likely needed for efficient NER.\n" ], "offsets": [ [ 0, 1377 ] ] } ]

[ { "id": "PMID-16082210_T1", "type": "Protein", "text": [ "Histone" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "PMID-16082210_T2", "type": "Protein", "text": [ "MFA2" ], "offsets": [ [ 98, 102 ] ], "normalized": [] }, { "id": "PMID-16082210_T3", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 485, 492 ] ], "normalized": [] }, { "id": "PMID-16082210_T4", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 583, 590 ] ], "normalized": [] }, { "id": "PMID-16082210_T5", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 616, 626 ] ], "normalized": [] }, { "id": "PMID-16082210_T6", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 631, 633 ] ], "normalized": [] }, { "id": "PMID-16082210_T7", "type": "Protein", "text": [ "MFA2" ], "offsets": [ [ 676, 680 ] ], "normalized": [] }, { "id": "PMID-16082210_T8", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 695, 705 ] ], "normalized": [] }, { "id": "PMID-16082210_T9", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 715, 725 ] ], "normalized": [] }, { "id": "PMID-16082210_T10", "type": "Protein", "text": [ "Gcn5p" ], "offsets": [ [ 765, 770 ] ], "normalized": [] }, { "id": "PMID-16082210_T11", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 780, 790 ] ], "normalized": [] }, { "id": "PMID-16082210_T12", "type": "Protein", "text": [ "MFA2" ], "offsets": [ [ 833, 837 ] ], "normalized": [] }, { "id": "PMID-16082210_T13", "type": "Protein", "text": [ "Gcn5p" ], "offsets": [ [ 930, 935 ] ], "normalized": [] }, { "id": "PMID-16082210_T14", "type": "Protein", "text": [ "Swi2p" ], "offsets": [ [ 970, 975 ] ], "normalized": [] }, { "id": "PMID-16082210_T15", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1061, 1068 ] ], "normalized": [] }, { "id": "PMID-16082210_T16", "type": "Protein", "text": [ "MFA2" ], "offsets": [ [ 1126, 1130 ] ], "normalized": [] }, { "id": "PMID-16082210_T17", "type": "Protein", "text": [ "MFA2" ], "offsets": [ [ 1156, 1160 ] ], "normalized": [] }, { "id": "PMID-16082210_T18", "type": "Protein", "text": [ "Rad4p" ], "offsets": [ [ 1218, 1223 ] ], "normalized": [] }, { "id": "PMID-16082210_T19", "type": "Protein", "text": [ "Rad14p" ], "offsets": [ [ 1227, 1233 ] ], "normalized": [] } ]

[ { "id": "PMID-16082210_E1", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 8, 19 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16082210_T1" } ] }, { "id": "PMID-16082210_E2", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 493, 504 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16082210_T3" } ] }, { "id": "PMID-16082210_E3", "type": "Acetylation", "trigger": { "text": [ "hyperacetylation" ], "offsets": [ [ 591, 607 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16082210_T5" } ] }, { "id": "PMID-16082210_E4", "type": "Acetylation", "trigger": { "text": [ "hyperacetylation" ], "offsets": [ [ 591, 607 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16082210_T6" } ] }, { "id": "PMID-16082210_E5", "type": "Acetylation", "trigger": { "text": [ "hyperacetylation" ], "offsets": [ [ 591, 607 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16082210_T4" } ] }, { "id": "PMID-16082210_E6", "type": "Acetylation", "trigger": { "text": [ "hyperacetylated" ], "offsets": [ [ 730, 745 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16082210_T8" }, { "role": "Contextgene", "ref_id": "PMID-16082210_T7" } ] }, { "id": "PMID-16082210_E7", "type": "Acetylation", "trigger": { "text": [ "hyperacetylated" ], "offsets": [ [ 730, 745 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16082210_T9" } ] }, { "id": "PMID-16082210_E8", "type": "Catalysis", "trigger": { "text": [ "mediated" ], "offsets": [ [ 771, 779 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16082210_E9" }, { "role": "Cause", "ref_id": "PMID-16082210_T10" } ] }, { "id": "PMID-16082210_E9", "type": "Acetylation", "trigger": { "text": [ "hyperacetylation" ], "offsets": [ [ 791, 807 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16082210_T11" }, { "role": "Contextgene", "ref_id": "PMID-16082210_T12" } ] } ]

[]

[]

[ { "id": "PMID-16099169__text", "type": "abstract", "text": [ "Peptide mass mapping of acetylated isoforms of histone H4 from mouse lymphosarcoma cells treated with histone deacetylase (HDACs) inhibitors. \nThe acetylated isoforms of histone H4 from mouse lymphosarcoma cells treated with HDAC inhibitors trichostatin A (TSA) and depsipeptide (DDP) were separated by acetic acid urea-polyacrylamide gel electrophoresis (AU-PAGE), in-gel digested, and analyzed by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS). The acetylation pattern of histone H4 in mouse lymphosarcoma cells induced by TSA was established in which acetylation initially occurred at K16 followed by K12 and then K8 and/or K5. An identical order of acetylation was found for cells treated with DDP.\n" ], "offsets": [ [ 0, 810 ] ] } ]

[ { "id": "PMID-16099169_T1", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 47, 57 ] ], "normalized": [] }, { "id": "PMID-16099169_T2", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 102, 109 ] ], "normalized": [] }, { "id": "PMID-16099169_T3", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 170, 180 ] ], "normalized": [] }, { "id": "PMID-16099169_T4", "type": "Protein", "text": [ "histone H4" ], "offsets": [ [ 581, 591 ] ], "normalized": [] }, { "id": "PMID-16099169_T9", "type": "Entity", "text": [ "K16" ], "offsets": [ [ 695, 698 ] ], "normalized": [] }, { "id": "PMID-16099169_T10", "type": "Entity", "text": [ "K12" ], "offsets": [ [ 711, 714 ] ], "normalized": [] }, { "id": "PMID-16099169_T11", "type": "Entity", "text": [ "K8" ], "offsets": [ [ 724, 726 ] ], "normalized": [] }, { "id": "PMID-16099169_T12", "type": "Entity", "text": [ "K5" ], "offsets": [ [ 734, 736 ] ], "normalized": [] } ]

[ { "id": "PMID-16099169_E1", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 24, 34 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16099169_T1" } ] }, { "id": "PMID-16099169_E2", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 147, 157 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16099169_T3" } ] }, { "id": "PMID-16099169_E3", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 558, 569 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16099169_T4" } ] }, { "id": "PMID-16099169_E4", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 661, 672 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16099169_T4" }, { "role": "Site", "ref_id": "PMID-16099169_T9" } ] }, { "id": "PMID-16099169_E5", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 661, 672 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16099169_T4" }, { "role": "Site", "ref_id": "PMID-16099169_T10" } ] }, { "id": "PMID-16099169_E6", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 661, 672 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16099169_T4" }, { "role": "Site", "ref_id": "PMID-16099169_T11" } ] }, { "id": "PMID-16099169_E7", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 661, 672 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16099169_T4" }, { "role": "Site", "ref_id": "PMID-16099169_T12" } ] }, { "id": "PMID-16099169_E8", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 760, 771 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16099169_T4" } ] } ]

[]

[]

[ { "id": "PMID-16135558__text", "type": "abstract", "text": [ "ST6GalNAc I expression in MDA-MB-231 breast cancer cells greatly modifies their O-glycosylation pattern and enhances their tumourigenicity. \nSialyl-Tn is a carbohydrate antigen overexpressed in several epithelial cancers, including breast cancer, and usually associated with poor prognosis. Sialyl-Tn is synthesized by a CMP-Neu5Ac:GalNAcalpha2,6-sialyltransferase: CMP-Neu5Ac: R-GalNAcalpha1-O-Ser/Thr alpha2,6-sialyltransferase (EC 2.4.99.3) (ST6GalNAc I), which transfers a sialic acid residue in alpha2,6-linkage to the GalNAcalpha1-O-Ser/Thr structure. However, established breast cancer cell lines express neither ST6GalNAc I nor sialyl-Tn. We have previously shown that stable transfection of MDA-MB-231, a human breast cancer cell line, with ST6GalNAc I cDNA induces sialyl-Tn antigen (STn) expression. We report here the modifications of the O-glycosylation pattern of a MUC1-related recombinant protein secreted by MDA-MB-231 sialyl-Tn positive cells. We also show that sialyl-Tn expression and concomitant changes in the overall O-glycan profiles induce a decrease of adhesion and an increase of migration of MDA-MB-231. Moreover, STn positive clones exhibit an increased tumour growth in severe combined immunodeficiency (SCID) mice. These observations suggest that modification of the O-glycosylation pattern induced by ST6GalNAc I expression are sufficient to enhance the tumourigenicity of MDA-MB-231 breast cancer cells.\n" ], "offsets": [ [ 0, 1437 ] ] } ]

[ { "id": "PMID-16135558_T1", "type": "Protein", "text": [ "ST6GalNAc I" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "PMID-16135558_T2", "type": "Protein", "text": [ "ST6GalNAc I" ], "offsets": [ [ 445, 456 ] ], "normalized": [] }, { "id": "PMID-16135558_T3", "type": "Protein", "text": [ "ST6GalNAc I" ], "offsets": [ [ 620, 631 ] ], "normalized": [] }, { "id": "PMID-16135558_T4", "type": "Protein", "text": [ "ST6GalNAc I" ], "offsets": [ [ 750, 761 ] ], "normalized": [] }, { "id": "PMID-16135558_T5", "type": "Protein", "text": [ "MUC1" ], "offsets": [ [ 880, 884 ] ], "normalized": [] }, { "id": "PMID-16135558_T6", "type": "Protein", "text": [ "ST6GalNAc I" ], "offsets": [ [ 1333, 1344 ] ], "normalized": [] } ]

[ { "id": "PMID-16135558_E1", "type": "Glycosylation", "trigger": { "text": [ "O-glycosylation" ], "offsets": [ [ 851, 866 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16135558_T5" } ] } ]

[]

[]

[ { "id": "PMID-16140212__text", "type": "abstract", "text": [ "NO restores HIF-1alpha hydroxylation during hypoxia: role of reactive oxygen species. \nThe activity of hypoxia-inducible factor 1 (HIF-1) is primarily determined by stability regulation of its alpha subunit, which is stabilized under hypoxia but degraded during normoxia. Hydroxylation of HIF-1alpha by prolyl hydroxylases (PHDs) recruits the von Hippel-Lindau (pVHL) E3 ubiquitin ligase complex to initiate proteolytic destruction of the alpha subunit. Hypoxic stabilization of HIF-1alpha has been reported to be antagonized by nitric oxide (NO). By using a HIF-1alpha-pVHL binding assay, we show that NO released from DETA-NO restored prolyl hydroxylase activity under hypoxia. Destabilization of HIF-1alpha by DETA-NO was reversed by free radical scavengers such as NAC and Tiron, thus pointing to the involvement of reactive oxygen species (ROS). Therefore, we examined the effects of ROS on HIF-1alpha stabilization. Treatment of cells under hypoxia with low concentrations of the superoxide generator 2,3-dimethoxy-1,4-naphthoquinone lowered HIF-1alpha protein stabilization. In vitro HIF-1alpha-pVHL interaction assays demonstrated that low-level ROS formation increased prolyl hydroxylase activity, an effect antagonized by ROS scavengers. While determining intracellular ROS formation we noticed that reduced ROS production under hypoxia was restored by the addition of DETA-NO. We propose that an increase in ROS formation contributes to HIF-1alpha destabilization by NO donors under hypoxia via modulation of PHD activity.\n" ], "offsets": [ [ 0, 1534 ] ] } ]

[ { "id": "PMID-16140212_T1", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 12, 22 ] ], "normalized": [] }, { "id": "PMID-16140212_T2", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 289, 299 ] ], "normalized": [] }, { "id": "PMID-16140212_T3", "type": "Protein", "text": [ "von Hippel-Lindau" ], "offsets": [ [ 343, 360 ] ], "normalized": [] }, { "id": "PMID-16140212_T4", "type": "Protein", "text": [ "pVHL" ], "offsets": [ [ 362, 366 ] ], "normalized": [] }, { "id": "PMID-16140212_T5", "type": "Protein", "text": [ "ubiquitin" ], "offsets": [ [ 371, 380 ] ], "normalized": [] }, { "id": "PMID-16140212_T6", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 479, 489 ] ], "normalized": [] }, { "id": "PMID-16140212_T7", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 559, 569 ] ], "normalized": [] }, { "id": "PMID-16140212_T8", "type": "Protein", "text": [ "pVHL" ], "offsets": [ [ 570, 574 ] ], "normalized": [] }, { "id": "PMID-16140212_T9", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 699, 709 ] ], "normalized": [] }, { "id": "PMID-16140212_T10", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 896, 906 ] ], "normalized": [] }, { "id": "PMID-16140212_T11", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1048, 1058 ] ], "normalized": [] }, { "id": "PMID-16140212_T12", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1091, 1101 ] ], "normalized": [] }, { "id": "PMID-16140212_T13", "type": "Protein", "text": [ "pVHL" ], "offsets": [ [ 1102, 1106 ] ], "normalized": [] }, { "id": "PMID-16140212_T14", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1448, 1458 ] ], "normalized": [] } ]

[ { "id": "PMID-16140212_E1", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 23, 36 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16140212_T1" } ] }, { "id": "PMID-16140212_E2", "type": "Hydroxylation", "trigger": { "text": [ "Hydroxylation" ], "offsets": [ [ 272, 285 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16140212_T2" } ] } ]

[ { "id": "PMID-16140212_1", "entity_ids": [ "PMID-16140212_T3", "PMID-16140212_T4" ] } ]

[]

[ { "id": "PMID-16150804__text", "type": "abstract", "text": [ "Functional relevance of ceruloplasmin mutations in Parkinson's disease. \nIncreased iron levels of the substantia nigra and the discovery of ceruloplasmin mutations in patients with Parkinson's disease (PD) imply impaired iron metabolism in this neurodegenerative disorder. Ceruloplasmin has ferroxidase activity oxidizing iron(II) to iron(III). In the present study, we analyzed the amount of ceruloplasmin, iron, ferritin, and transferrin and the ceruloplasmin ferroxidase activity in serum of patients with the diagnosis of PD carrying the ceruloplasmin mutations I63T, D544E, and R793H. The impact of these missense mutations on the biosynthesis of holo-ceruloplasmin was investigated in cell culture experiments. Functional relevance was found for the ceruloplasmin mutations I63T and D544E. In vivo, the I63T mutation resulted in half the normal ceruloplasmin concentration and markedly reduced ferroxidase activity in serum from a heteroallelic PD patient. In cell culture, the I63T glycosylphosphatidylinositol (GPI)-linked ceruloplasmin isoform was retained in the endoplasmatic reticulum of human embryonic kidney cells. Furthermore, the D544E polymorphism resulted in significantly reduced serum ceruloplasmin levels and ferroxidase activity in heteroallelic patients and in expression of mainly apo-ceruloplasmin in cell culture. Our studies indicate that altered activity of ceruloplasmin may present a vulnerability factor for iron induced oxidative stress in PD.\n" ], "offsets": [ [ 0, 1477 ] ] } ]

[ { "id": "PMID-16150804_T1", "type": "Protein", "text": [ "ceruloplasmin" ], "offsets": [ [ 24, 37 ] ], "normalized": [] }, { "id": "PMID-16150804_T2", "type": "Protein", "text": [ "ceruloplasmin" ], "offsets": [ [ 140, 153 ] ], "normalized": [] }, { "id": "PMID-16150804_T3", "type": "Protein", "text": [ "Ceruloplasmin" ], "offsets": [ [ 273, 286 ] ], "normalized": [] }, { "id": "PMID-16150804_T4", "type": "Protein", "text": [ "ceruloplasmin" ], "offsets": [ [ 393, 406 ] ], "normalized": [] }, { "id": "PMID-16150804_T5", "type": "Protein", "text": [ "ferritin" ], "offsets": [ [ 414, 422 ] ], "normalized": [] }, { "id": "PMID-16150804_T6", "type": "Protein", "text": [ "transferrin" ], "offsets": [ [ 428, 439 ] ], "normalized": [] }, { "id": "PMID-16150804_T7", "type": "Protein", "text": [ "ceruloplasmin" ], "offsets": [ [ 448, 461 ] ], "normalized": [] }, { "id": "PMID-16150804_T8", "type": "Protein", "text": [ "ceruloplasmin" ], "offsets": [ [ 542, 555 ] ], "normalized": [] }, { "id": "PMID-16150804_T9", "type": "Protein", "text": [ "ceruloplasmin" ], "offsets": [ [ 657, 670 ] ], "normalized": [] }, { "id": "PMID-16150804_T10", "type": "Protein", "text": [ "ceruloplasmin" ], "offsets": [ [ 756, 769 ] ], "normalized": [] }, { "id": "PMID-16150804_T11", "type": "Protein", "text": [ "ceruloplasmin" ], "offsets": [ [ 851, 864 ] ], "normalized": [] }, { "id": "PMID-16150804_T12", "type": "Protein", "text": [ "ceruloplasmin" ], "offsets": [ [ 1031, 1044 ] ], "normalized": [] }, { "id": "PMID-16150804_T13", "type": "Protein", "text": [ "ceruloplasmin" ], "offsets": [ [ 1206, 1219 ] ], "normalized": [] }, { "id": "PMID-16150804_T14", "type": "Protein", "text": [ "ceruloplasmin" ], "offsets": [ [ 1310, 1323 ] ], "normalized": [] }, { "id": "PMID-16150804_T15", "type": "Protein", "text": [ "ceruloplasmin" ], "offsets": [ [ 1387, 1400 ] ], "normalized": [] }, { "id": "PMID-16150804_T16", "type": "Entity", "text": [ "glycosylphosphatidylinositol" ], "offsets": [ [ 989, 1017 ] ], "normalized": [] }, { "id": "PMID-16150804_T17", "type": "Entity", "text": [ "GPI" ], "offsets": [ [ 1019, 1022 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-16150804_1", "entity_ids": [ "PMID-16150804_T16", "PMID-16150804_T17" ] } ]

[]

[ { "id": "PMID-16182243__text", "type": "abstract", "text": [ "A fluorescence polarization-based interaction assay for hypoxia-inducible factor prolyl hydroxylases. \nOxygen-dependent ubiquitination and degradation of hypoxia-inducible factor 1alpha (HIF-1alpha) plays a central role in regulating transcriptional responses to hypoxia. This process requires hydroxylation of specific prolines in HIF-1alpha by HIF prolyl hydroxylase domain (PHD)-containing enzymes, leading to its specific interactions with von Hippel-Lindau protein-Elongin B-Elongin C (VBC). Here we describe a straightforward approach to apply these interactions to measure PHD activities. Employing fluorescently labeled HIF-1alpha peptides containing hydroxyproline, we developed a quantitative method based on fluorescence polarization for a systematic evaluation of binding of hydroxylated HIF-1alpha to recombinant VBC. The method was then successfully utilized for measuring the activity of the truncated, purified PHD2. The applicability of the assay was further demonstrated by examining effects of various cofactors and inhibitors for PHD2. The developed homogeneous assay would provide a convenient way of probing the biochemical properties of the HIF-1alpha-VBC interaction and PHDs, and of screening modulators for the interaction as well as the enzyme.\n" ], "offsets": [ [ 0, 1272 ] ] } ]

[ { "id": "PMID-16182243_T1", "type": "Protein", "text": [ "hypoxia-inducible factor 1alpha" ], "offsets": [ [ 154, 185 ] ], "normalized": [] }, { "id": "PMID-16182243_T2", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 187, 197 ] ], "normalized": [] }, { "id": "PMID-16182243_T3", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 332, 342 ] ], "normalized": [] }, { "id": "PMID-16182243_T4", "type": "Protein", "text": [ "von Hippel-Lindau" ], "offsets": [ [ 444, 461 ] ], "normalized": [] }, { "id": "PMID-16182243_T5", "type": "Protein", "text": [ "Elongin B" ], "offsets": [ [ 470, 479 ] ], "normalized": [] }, { "id": "PMID-16182243_T6", "type": "Protein", "text": [ "Elongin C" ], "offsets": [ [ 480, 489 ] ], "normalized": [] }, { "id": "PMID-16182243_T7", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 628, 638 ] ], "normalized": [] }, { "id": "PMID-16182243_T8", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 800, 810 ] ], "normalized": [] }, { "id": "PMID-16182243_T9", "type": "Protein", "text": [ "PHD2" ], "offsets": [ [ 927, 931 ] ], "normalized": [] }, { "id": "PMID-16182243_T10", "type": "Protein", "text": [ "PHD2" ], "offsets": [ [ 1050, 1054 ] ], "normalized": [] }, { "id": "PMID-16182243_T11", "type": "Protein", "text": [ "HIF-1alpha" ], "offsets": [ [ 1164, 1174 ] ], "normalized": [] }, { "id": "PMID-16182243_T14", "type": "Entity", "text": [ "prolines" ], "offsets": [ [ 320, 328 ] ], "normalized": [] } ]

[ { "id": "PMID-16182243_E1", "type": "Ubiquitination", "trigger": { "text": [ "ubiquitination" ], "offsets": [ [ 120, 134 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16182243_T1" } ] }, { "id": "PMID-16182243_E2", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 294, 307 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16182243_T3" }, { "role": "Site", "ref_id": "PMID-16182243_T14" } ] }, { "id": "PMID-16182243_E3", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylated" ], "offsets": [ [ 787, 799 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16182243_T8" } ] } ]

[ { "id": "PMID-16182243_1", "entity_ids": [ "PMID-16182243_T1", "PMID-16182243_T2" ] } ]

[]

[ { "id": "PMID-16210620__text", "type": "abstract", "text": [ "Protein acetylation regulates both PU.1 transactivation and Ig kappa 3' enhancer activity. \nIgkappa gene expression and chromatin structure change during B cell development. At the pre-B cell stage, the locus is relatively hypoacetylated on histone H3, whereas it is hyperacetylated at the plasma cell stage. We find in this study that the histone deacetylase inhibitor, trichostatin A (TSA) stimulated 3' enhancer activity through the PU.1 binding site. TSA also stimulated PU.1 transactivation potential. PU.1 activity was increased by the coactivator acetyltransferase protein, p300, and p300 physically interacted with PU.1 residues 7-30. PU.1 served as a substrate for p300 and was acetylated on lysine residues 170, 171, 206, and 208. Mutation of PU.1 lysines 170 and 171 did not affect PU.1 DNA binding, but did lower the ability of PU.1 to activate transcription in association with p300. Lysine 170 was acetylated in pre-B cells and plasmacytoma cells, but TSA treatment did not stimulate PU.1 acetylation at this residue arguing that a second mechanism can stimulate 3' enhancer activity. Using chromatin immunoprecipitation assays we found that TSA caused preferential acetylation of histone H3 at the 3' enhancer. The relevance of these studies for PU.1 function in transcription and hemopoietic development is discussed.\n" ], "offsets": [ [ 0, 1334 ] ] } ]

[ { "id": "PMID-16210620_T1", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 35, 39 ] ], "normalized": [] }, { "id": "PMID-16210620_T2", "type": "Protein", "text": [ "Ig kappa" ], "offsets": [ [ 60, 68 ] ], "normalized": [] }, { "id": "PMID-16210620_T3", "type": "Protein", "text": [ "Igkappa" ], "offsets": [ [ 92, 99 ] ], "normalized": [] }, { "id": "PMID-16210620_T4", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 241, 251 ] ], "normalized": [] }, { "id": "PMID-16210620_T5", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 340, 347 ] ], "normalized": [] }, { "id": "PMID-16210620_T6", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 436, 440 ] ], "normalized": [] }, { "id": "PMID-16210620_T7", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 475, 479 ] ], "normalized": [] }, { "id": "PMID-16210620_T8", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 507, 511 ] ], "normalized": [] }, { "id": "PMID-16210620_T9", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 581, 585 ] ], "normalized": [] }, { "id": "PMID-16210620_T10", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 591, 595 ] ], "normalized": [] }, { "id": "PMID-16210620_T11", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 623, 627 ] ], "normalized": [] }, { "id": "PMID-16210620_T12", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 643, 647 ] ], "normalized": [] }, { "id": "PMID-16210620_T13", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 674, 678 ] ], "normalized": [] }, { "id": "PMID-16210620_T14", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 753, 757 ] ], "normalized": [] }, { "id": "PMID-16210620_T15", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 793, 797 ] ], "normalized": [] }, { "id": "PMID-16210620_T16", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 840, 844 ] ], "normalized": [] }, { "id": "PMID-16210620_T17", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 891, 895 ] ], "normalized": [] }, { "id": "PMID-16210620_T18", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 998, 1002 ] ], "normalized": [] }, { "id": "PMID-16210620_T19", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 1195, 1205 ] ], "normalized": [] }, { "id": "PMID-16210620_T20", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1261, 1265 ] ], "normalized": [] }, { "id": "PMID-16210620_T25", "type": "Entity", "text": [ "lysine residues 170" ], "offsets": [ [ 701, 720 ] ], "normalized": [] }, { "id": "PMID-16210620_T26", "type": "Entity", "text": [ "171" ], "offsets": [ [ 722, 725 ] ], "normalized": [] }, { "id": "PMID-16210620_T27", "type": "Entity", "text": [ "206" ], "offsets": [ [ 727, 730 ] ], "normalized": [] }, { "id": "PMID-16210620_T28", "type": "Entity", "text": [ "208" ], "offsets": [ [ 736, 739 ] ], "normalized": [] }, { "id": "PMID-16210620_T29", "type": "Entity", "text": [ "Lysine 170" ], "offsets": [ [ 897, 907 ] ], "normalized": [] } ]

[ { "id": "PMID-16210620_E1", "type": "Acetylation", "trigger": { "text": [ "hypoacetylated" ], "offsets": [ [ 223, 237 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_T4" }, { "role": "Contextgene", "ref_id": "PMID-16210620_T3" } ] }, { "id": "PMID-16210620_E2", "type": "Acetylation", "trigger": { "text": [ "hyperacetylated" ], "offsets": [ [ 267, 282 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_T4" }, { "role": "Contextgene", "ref_id": "PMID-16210620_T3" } ] }, { "id": "PMID-16210620_E3", "type": "Catalysis", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 687, 697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_E10" }, { "role": "Cause", "ref_id": "PMID-16210620_T13" } ] }, { "id": "PMID-16210620_E4", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 687, 697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_T12" }, { "role": "Site", "ref_id": "PMID-16210620_T25" } ] }, { "id": "PMID-16210620_E5", "type": "Catalysis", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 687, 697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_E4" }, { "role": "Cause", "ref_id": "PMID-16210620_T13" } ] }, { "id": "PMID-16210620_E6", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 687, 697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_T12" }, { "role": "Site", "ref_id": "PMID-16210620_T26" } ] }, { "id": "PMID-16210620_E7", "type": "Catalysis", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 687, 697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_E6" }, { "role": "Cause", "ref_id": "PMID-16210620_T13" } ] }, { "id": "PMID-16210620_E8", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 687, 697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_T12" }, { "role": "Site", "ref_id": "PMID-16210620_T27" } ] }, { "id": "PMID-16210620_E9", "type": "Catalysis", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 687, 697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_E8" }, { "role": "Cause", "ref_id": "PMID-16210620_T13" } ] }, { "id": "PMID-16210620_E10", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 687, 697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_T12" }, { "role": "Site", "ref_id": "PMID-16210620_T28" } ] }, { "id": "PMID-16210620_E11", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 912, 922 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_T18" }, { "role": "Site", "ref_id": "PMID-16210620_T29" } ] }, { "id": "PMID-16210620_E12", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 1003, 1014 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_T18" } ] }, { "id": "PMID-16210620_E13", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 1180, 1191 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16210620_T19" }, { "role": "Contextgene", "ref_id": "PMID-16210620_T3" } ] } ]

[]

[]

[ { "id": "PMID-16248853__text", "type": "abstract", "text": [ "Dual promoters control the cell-specific expression of the human cell death-inducing DFF45-like effector B gene. \nCIDE-B [cell death-inducing DFF45 (DNA fragmentation factor 45)-like effector B] is a member of the CIDE family of apoptosis-inducing factors. The highly restricted pattern of expression of CIDE-B in the liver and spleen suggests that a mechanism exists for the tissue- and cell-specific regulation of transcription of this gene. We have analysed the promoters of the human CIDE-B gene, particularly the mechanism of cell-specific transcription. Expression of CIDE-B is driven by two promoters which are responsible for the synthesis of two types of transcript, and Sp1 and Sp3 are key regulators of basal transcription from both the upstream and the internal promoter, as indicated by EMSAs (electrophoretic mobility-shift assays) and site-directed mutagenesis. Bisulphite sequencing analysis demonstrated that the upstream promoter was hypermethylated in cells that did not express the long transcript of CIDE-B, but was hypomethylated in cells that expressed this transcript. Furthermore, methylation of this region in vitro reduced the promoter activity to approximately 5% of the control. Thus methylation at CpG sites in the upstream promoter region appeared to be important for cell-specific synthesis of the long transcript. By contrast, HNF4alpha (hepatocyte nuclear factor-4alpha) bound to the internal promoter and enhanced its activity. Moreover, the short transcript of CIDE-B gene was expressed in cells which do not normally express this transcript upon introduction of exogenous HNF4alpha, demonstrating the involvement of HNF4alpha in the cell-specific synthesis of the short transcript. Thus our analysis revealed a novel mechanism for the cell-specific transcription of the human CIDE-B gene, which involves epigenetic and genetic control at separate respective promoters.\n" ], "offsets": [ [ 0, 1906 ] ] } ]

[ { "id": "PMID-16248853_T1", "type": "Protein", "text": [ "cell death-inducing DFF45-like effector B" ], "offsets": [ [ 65, 106 ] ], "normalized": [] }, { "id": "PMID-16248853_T2", "type": "Protein", "text": [ "CIDE-B" ], "offsets": [ [ 114, 120 ] ], "normalized": [] }, { "id": "PMID-16248853_T3", "type": "Protein", "text": [ "cell death-inducing DFF45 (DNA fragmentation factor 45)-like effector B" ], "offsets": [ [ 122, 193 ] ], "normalized": [] }, { "id": "PMID-16248853_T4", "type": "Protein", "text": [ "CIDE-B" ], "offsets": [ [ 304, 310 ] ], "normalized": [] }, { "id": "PMID-16248853_T5", "type": "Protein", "text": [ "CIDE-" ], "offsets": [ [ 488, 493 ] ], "normalized": [] }, { "id": "PMID-16248853_T6", "type": "Protein", "text": [ "CIDE-B" ], "offsets": [ [ 574, 580 ] ], "normalized": [] }, { "id": "PMID-16248853_T7", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 680, 683 ] ], "normalized": [] }, { "id": "PMID-16248853_T8", "type": "Protein", "text": [ "Sp3" ], "offsets": [ [ 688, 691 ] ], "normalized": [] }, { "id": "PMID-16248853_T9", "type": "Protein", "text": [ "CIDE-B" ], "offsets": [ [ 1021, 1027 ] ], "normalized": [] }, { "id": "PMID-16248853_T10", "type": "Protein", "text": [ "HNF4alpha" ], "offsets": [ [ 1360, 1369 ] ], "normalized": [] }, { "id": "PMID-16248853_T11", "type": "Protein", "text": [ "hepatocyte nuclear factor-4alpha" ], "offsets": [ [ 1371, 1403 ] ], "normalized": [] }, { "id": "PMID-16248853_T12", "type": "Protein", "text": [ "CIDE-B" ], "offsets": [ [ 1497, 1503 ] ], "normalized": [] }, { "id": "PMID-16248853_T13", "type": "Protein", "text": [ "HNF4alpha" ], "offsets": [ [ 1609, 1618 ] ], "normalized": [] }, { "id": "PMID-16248853_T14", "type": "Protein", "text": [ "HNF4alpha" ], "offsets": [ [ 1653, 1662 ] ], "normalized": [] }, { "id": "PMID-16248853_T15", "type": "Protein", "text": [ "CIDE-B" ], "offsets": [ [ 1813, 1819 ] ], "normalized": [] }, { "id": "PMID-16248853_T16", "type": "Entity", "text": [ "upstream promoter" ], "offsets": [ [ 930, 947 ] ], "normalized": [] }, { "id": "PMID-16248853_T21", "type": "Entity", "text": [ "CpG sites" ], "offsets": [ [ 1228, 1237 ] ], "normalized": [] } ]

[ { "id": "PMID-16248853_E1", "type": "DNA_methylation", "trigger": { "text": [ "hypermethylated" ], "offsets": [ [ 952, 967 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16248853_T9" }, { "role": "Site", "ref_id": "PMID-16248853_T16" } ] }, { "id": "PMID-16248853_E2", "type": "DNA_methylation", "trigger": { "text": [ "hypomethylated" ], "offsets": [ [ 1037, 1051 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16248853_T9" }, { "role": "Site", "ref_id": "PMID-16248853_T16" } ] }, { "id": "PMID-16248853_E3", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1106, 1117 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16248853_T9" }, { "role": "Site", "ref_id": "PMID-16248853_T16" } ] }, { "id": "PMID-16248853_E4", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1213, 1224 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16248853_T9" }, { "role": "Site", "ref_id": "PMID-16248853_T21" } ] } ]

[ { "id": "PMID-16248853_1", "entity_ids": [ "PMID-16248853_T2", "PMID-16248853_T3" ] }, { "id": "PMID-16248853_2", "entity_ids": [ "PMID-16248853_T10", "PMID-16248853_T11" ] } ]

[]

[ { "id": "PMID-16263726__text", "type": "abstract", "text": [ "Human but not yeast CHD1 binds directly and selectively to histone H3 methylated at lysine 4 via its tandem chromodomains. \nDefining the protein factors that directly recognize post-translational, covalent histone modifications is essential toward understanding the impact of these chromatin \"marks\" on gene regulation. In the current study, we identify human CHD1, an ATP-dependent chromatin remodeling protein, as a factor that directly and selectively recognizes histone H3 methylated on lysine 4. In vitro binding studies identified that CHD1 recognizes di- and trimethyl H3K4 with a dissociation constant (Kd) of approximately 5 microm, whereas monomethyl H3K4 binds CHD1 with a 3-fold lower affinity. Surprisingly, human CHD1 binds to methylated H3K4 in a manner that requires both of its tandem chromodomains. In vitro analyses demonstrate that unlike human CHD1, yeast Chd1 does not bind methylated H3K4. Our findings indicate that yeast and human CHD1 have diverged in their ability to discriminate covalently modified histones and link histone modification-recognition and non-covalent chromatin remodeling activities within a single human protein.\n" ], "offsets": [ [ 0, 1159 ] ] } ]

[ { "id": "PMID-16263726_T1", "type": "Protein", "text": [ "CHD1" ], "offsets": [ [ 20, 24 ] ], "normalized": [] }, { "id": "PMID-16263726_T2", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 59, 69 ] ], "normalized": [] }, { "id": "PMID-16263726_T3", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 206, 213 ] ], "normalized": [] }, { "id": "PMID-16263726_T4", "type": "Protein", "text": [ "CHD1" ], "offsets": [ [ 360, 364 ] ], "normalized": [] }, { "id": "PMID-16263726_T5", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 466, 476 ] ], "normalized": [] }, { "id": "PMID-16263726_T6", "type": "Protein", "text": [ "CHD1" ], "offsets": [ [ 542, 546 ] ], "normalized": [] }, { "id": "PMID-16263726_T7", "type": "Protein", "text": [ "CHD1" ], "offsets": [ [ 672, 676 ] ], "normalized": [] }, { "id": "PMID-16263726_T8", "type": "Protein", "text": [ "CHD1" ], "offsets": [ [ 727, 731 ] ], "normalized": [] }, { "id": "PMID-16263726_T9", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 752, 754 ] ], "normalized": [] }, { "id": "PMID-16263726_T10", "type": "Protein", "text": [ "CHD1" ], "offsets": [ [ 865, 869 ] ], "normalized": [] }, { "id": "PMID-16263726_T11", "type": "Protein", "text": [ "Chd1" ], "offsets": [ [ 877, 881 ] ], "normalized": [] }, { "id": "PMID-16263726_T12", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 907, 909 ] ], "normalized": [] }, { "id": "PMID-16263726_T13", "type": "Protein", "text": [ "CHD1" ], "offsets": [ [ 956, 960 ] ], "normalized": [] }, { "id": "PMID-16263726_T14", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 1028, 1036 ] ], "normalized": [] }, { "id": "PMID-16263726_T15", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 1046, 1053 ] ], "normalized": [] }, { "id": "PMID-16263726_T17", "type": "Entity", "text": [ "lysine 4" ], "offsets": [ [ 84, 92 ] ], "normalized": [] }, { "id": "PMID-16263726_T19", "type": "Entity", "text": [ "lysine 4" ], "offsets": [ [ 491, 499 ] ], "normalized": [] }, { "id": "PMID-16263726_T21", "type": "Entity", "text": [ "K4" ], "offsets": [ [ 754, 756 ] ], "normalized": [] }, { "id": "PMID-16263726_T23", "type": "Entity", "text": [ "K4" ], "offsets": [ [ 909, 911 ] ], "normalized": [] } ]

[ { "id": "PMID-16263726_E1", "type": "Methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 70, 80 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16263726_T2" }, { "role": "Site", "ref_id": "PMID-16263726_T17" } ] }, { "id": "PMID-16263726_E2", "type": "Methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 477, 487 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16263726_T5" }, { "role": "Site", "ref_id": "PMID-16263726_T19" } ] }, { "id": "PMID-16263726_E3", "type": "Methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 741, 751 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16263726_T9" }, { "role": "Site", "ref_id": "PMID-16263726_T21" } ] }, { "id": "PMID-16263726_E4", "type": "Methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 896, 906 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16263726_T12" }, { "role": "Site", "ref_id": "PMID-16263726_T23" } ] } ]

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[]

[ { "id": "PMID-16269334__text", "type": "abstract", "text": [ "The proteasome regulatory particle alters the SAGA coactivator to enhance its interactions with transcriptional activators. \nPromoter recruitment of the Saccharomyces cerevisiae SAGA histone acetyltransferase complex is required for RNA polymerase II-dependent transcription of several genes. SAGA is targeted to promoters through interactions with sequence-specific DNA binding transcriptional activators and facilitates preinitiation-complex assembly and transcription. Here, we show that the 19S proteasome regulatory particle (19S RP) alters SAGA to stimulate its interaction with transcriptional activators. The ATPase components of the 19S RP are required for stimulation of SAGA/activator interactions and enhance SAGA recruitment to promoters. Proteasomal ATPases genetically interact with SAGA, and their inhibition reduces global histone H3 acetylation levels and SAGA recruitment to target promoters in vivo. These results indicate that the 19S RP modulates SAGA complex using its ATPase components, thereby facilitating subsequent transcription events at promoters.\n" ], "offsets": [ [ 0, 1078 ] ] } ]

[ { "id": "PMID-16269334_T1", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 183, 190 ] ], "normalized": [] }, { "id": "PMID-16269334_T2", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 840, 850 ] ], "normalized": [] } ]

[ { "id": "PMID-16269334_E1", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 851, 862 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16269334_T2" } ] } ]

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[]

[ { "id": "PMID-16299497__text", "type": "abstract", "text": [ "Prevention of early flowering by expression of FLOWERING LOCUS C requires methylation of histone H3 K36. \nFlowering represents a crucial transition from a vegetative to a reproductive phase of the plant life cycle. Despite extensive studies, the molecular mechanisms controlling flowering remain elusive. Although the enzymes involved are unknown, methylation of histone H3 K9 and K27 correlates with repression of FLOWERING LOCUS C (FLC), an essential transcriptional repressor involved in flowering time control in Arabidopsis thaliana; in contrast, methylation of H3K4 correlates with FLC activation. Here we show that loss-of-function of SET DOMAIN GROUP 8 (SDG 8), which encodes a homologue of the yeast SET2 histone methyltransferase, results in reduced dimethylation of histone H3K36, particularly in chromatin associated with the FLC promoter and the first intron, regions that contain essential cis-elements for transcription. sdg8 mutants display reduced FLC expression and flower early, establishing SDG8-mediated H3K36 methylation as a novel epigenetic memory code required for FLC expression in preventing early flowering. This is the first demonstrated role of H3K36 methylation in eukaryote development.\n" ], "offsets": [ [ 0, 1219 ] ] } ]

[ { "id": "PMID-16299497_T1", "type": "Protein", "text": [ "FLOWERING LOCUS C" ], "offsets": [ [ 47, 64 ] ], "normalized": [] }, { "id": "PMID-16299497_T2", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 89, 99 ] ], "normalized": [] }, { "id": "PMID-16299497_T3", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 363, 373 ] ], "normalized": [] }, { "id": "PMID-16299497_T4", "type": "Protein", "text": [ "FLOWERING LOCUS C" ], "offsets": [ [ 415, 432 ] ], "normalized": [] }, { "id": "PMID-16299497_T5", "type": "Protein", "text": [ "FLC" ], "offsets": [ [ 434, 437 ] ], "normalized": [] }, { "id": "PMID-16299497_T6", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 567, 569 ] ], "normalized": [] }, { "id": "PMID-16299497_T7", "type": "Protein", "text": [ "FLC" ], "offsets": [ [ 588, 591 ] ], "normalized": [] }, { "id": "PMID-16299497_T8", "type": "Protein", "text": [ "SET DOMAIN GROUP 8" ], "offsets": [ [ 642, 660 ] ], "normalized": [] }, { "id": "PMID-16299497_T9", "type": "Protein", "text": [ "SDG 8" ], "offsets": [ [ 662, 667 ] ], "normalized": [] }, { "id": "PMID-16299497_T10", "type": "Protein", "text": [ "SET2" ], "offsets": [ [ 709, 713 ] ], "normalized": [] }, { "id": "PMID-16299497_T11", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 777, 787 ] ], "normalized": [] }, { "id": "PMID-16299497_T12", "type": "Protein", "text": [ "FLC" ], "offsets": [ [ 838, 841 ] ], "normalized": [] }, { "id": "PMID-16299497_T13", "type": "Protein", "text": [ "sdg8" ], "offsets": [ [ 936, 940 ] ], "normalized": [] }, { "id": "PMID-16299497_T14", "type": "Protein", "text": [ "FLC" ], "offsets": [ [ 965, 968 ] ], "normalized": [] }, { "id": "PMID-16299497_T15", "type": "Protein", "text": [ "SDG8" ], "offsets": [ [ 1011, 1015 ] ], "normalized": [] }, { "id": "PMID-16299497_T16", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1025, 1027 ] ], "normalized": [] }, { "id": "PMID-16299497_T17", "type": "Protein", "text": [ "FLC" ], "offsets": [ [ 1090, 1093 ] ], "normalized": [] }, { "id": "PMID-16299497_T18", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1175, 1177 ] ], "normalized": [] }, { "id": "PMID-16299497_T20", "type": "Entity", "text": [ "K36" ], "offsets": [ [ 100, 103 ] ], "normalized": [] }, { "id": "PMID-16299497_T22", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 374, 376 ] ], "normalized": [] }, { "id": "PMID-16299497_T23", "type": "Entity", "text": [ "K27" ], "offsets": [ [ 381, 384 ] ], "normalized": [] }, { "id": "PMID-16299497_T25", "type": "Entity", "text": [ "K4" ], "offsets": [ [ 569, 571 ] ], "normalized": [] }, { "id": "PMID-16299497_T27", "type": "Entity", "text": [ "K36" ], "offsets": [ [ 787, 790 ] ], "normalized": [] }, { "id": "PMID-16299497_T29", "type": "Entity", "text": [ "K36" ], "offsets": [ [ 1027, 1030 ] ], "normalized": [] }, { "id": "PMID-16299497_T31", "type": "Entity", "text": [ "K36" ], "offsets": [ [ 1177, 1180 ] ], "normalized": [] } ]

[ { "id": "PMID-16299497_E1", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 74, 85 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16299497_T2" }, { "role": "Site", "ref_id": "PMID-16299497_T20" }, { "role": "Contextgene", "ref_id": "PMID-16299497_T1" } ] }, { "id": "PMID-16299497_E2", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 348, 359 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16299497_T3" }, { "role": "Site", "ref_id": "PMID-16299497_T22" }, { "role": "Contextgene", "ref_id": "PMID-16299497_T4" } ] }, { "id": "PMID-16299497_E3", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 348, 359 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16299497_T3" }, { "role": "Site", "ref_id": "PMID-16299497_T23" }, { "role": "Contextgene", "ref_id": "PMID-16299497_T4" } ] }, { "id": "PMID-16299497_E4", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 552, 563 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16299497_T6" }, { "role": "Site", "ref_id": "PMID-16299497_T25" }, { "role": "Contextgene", "ref_id": "PMID-16299497_T7" } ] }, { "id": "PMID-16299497_E5", "type": "Methylation", "trigger": { "text": [ "dimethylation" ], "offsets": [ [ 760, 773 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16299497_T11" }, { "role": "Site", "ref_id": "PMID-16299497_T27" }, { "role": "Contextgene", "ref_id": "PMID-16299497_T12" } ] }, { "id": "PMID-16299497_E6", "type": "Catalysis", "trigger": { "text": [ "mediated" ], "offsets": [ [ 1016, 1024 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16299497_E7" }, { "role": "Cause", "ref_id": "PMID-16299497_T15" } ] }, { "id": "PMID-16299497_E7", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1031, 1042 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16299497_T16" }, { "role": "Site", "ref_id": "PMID-16299497_T29" }, { "role": "Contextgene", "ref_id": "PMID-16299497_T17" } ] }, { "id": "PMID-16299497_E8", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1181, 1192 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16299497_T18" }, { "role": "Site", "ref_id": "PMID-16299497_T31" } ] } ]

[ { "id": "PMID-16299497_1", "entity_ids": [ "PMID-16299497_T4", "PMID-16299497_T5" ] }, { "id": "PMID-16299497_2", "entity_ids": [ "PMID-16299497_T8", "PMID-16299497_T9" ] } ]

[]

[ { "id": "PMID-16314839__text", "type": "abstract", "text": [ "Loss of interleukin-2-dependency in HTLV-I-infected T cells on gene silencing of thioredoxin-binding protein-2. \nThe transition from interleukin-2 (IL-2)-dependent to IL-2-independent growth is considered one of the key steps in the transformation of human T-cell leukemia virus type-I (HTLV-I)-infected T cells. The expression of thioredoxin-binding protein-2 (TBP-2) is lost during the transition of HTLV-I-infected T-cell lines. Here, we analysed the mechanism of loss of TBP-2 expression and the role of TBP-2 in IL-2-dependent growth in the in vitro model to investigate multistep transformation of HTLV-I. CpGs in the TBP-2 gene are methylated in IL-2-independent but not in IL-2-dependent cells. Sequential treatment with 5-aza-2'-deoxycytidine and a histone deacetylase inhibitor augmented histone acetylation and TBP-2 expression, suggesting that loss of TBP-2 expression is due to DNA methylation and histone deacetylation. In IL-2-dependent cells, a basal level of TBP-2 expression was maintained by IL-2 associated with cellular growth, whereas TBP-2 expression was upregulated on deprivation of IL-2 associated with growth suppression. Overexpression of TBP-2 in IL-2-independent cells suppressed the growth and partially restored responsiveness to IL-2. Knockdown of TBP-2 caused the IL-2-dependent cells to show partial growth without IL-2. These results suggested that epigenetic silencing of the TBP-2 gene results in a loss of responsiveness to IL-2, contributing to uncontrolled IL-2-independent growth in HTLV-I-infected T-cell lines.\n" ], "offsets": [ [ 0, 1555 ] ] } ]

[ { "id": "PMID-16314839_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 8, 21 ] ], "normalized": [] }, { "id": "PMID-16314839_T2", "type": "Protein", "text": [ "thioredoxin-binding protein-2" ], "offsets": [ [ 81, 110 ] ], "normalized": [] }, { "id": "PMID-16314839_T3", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 133, 146 ] ], "normalized": [] }, { "id": "PMID-16314839_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 148, 152 ] ], "normalized": [] }, { "id": "PMID-16314839_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 167, 171 ] ], "normalized": [] }, { "id": "PMID-16314839_T6", "type": "Protein", "text": [ "thioredoxin-binding protein-2" ], "offsets": [ [ 331, 360 ] ], "normalized": [] }, { "id": "PMID-16314839_T7", "type": "Protein", "text": [ "TBP-2" ], "offsets": [ [ 362, 367 ] ], "normalized": [] }, { "id": "PMID-16314839_T8", "type": "Protein", "text": [ "TBP-2" ], "offsets": [ [ 475, 480 ] ], "normalized": [] }, { "id": "PMID-16314839_T9", "type": "Protein", "text": [ "TBP-2" ], "offsets": [ [ 508, 513 ] ], "normalized": [] }, { "id": "PMID-16314839_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 517, 521 ] ], "normalized": [] }, { "id": "PMID-16314839_T11", "type": "Protein", "text": [ "TBP-2" ], "offsets": [ [ 624, 629 ] ], "normalized": [] }, { "id": "PMID-16314839_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 653, 657 ] ], "normalized": [] }, { "id": "PMID-16314839_T13", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 681, 685 ] ], "normalized": [] }, { "id": "PMID-16314839_T14", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 758, 765 ] ], "normalized": [] }, { "id": "PMID-16314839_T15", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 798, 805 ] ], "normalized": [] }, { "id": "PMID-16314839_T16", "type": "Protein", "text": [ "TBP-2" ], "offsets": [ [ 822, 827 ] ], "normalized": [] }, { "id": "PMID-16314839_T17", "type": "Protein", "text": [ "TBP-2" ], "offsets": [ [ 864, 869 ] ], "normalized": [] }, { "id": "PMID-16314839_T18", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 911, 918 ] ], "normalized": [] }, { "id": "PMID-16314839_T19", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 937, 941 ] ], "normalized": [] }, { "id": "PMID-16314839_T20", "type": "Protein", "text": [ "TBP-2" ], "offsets": [ [ 976, 981 ] ], "normalized": [] }, { "id": "PMID-16314839_T21", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1011, 1015 ] ], "normalized": [] }, { "id": "PMID-16314839_T22", "type": "Protein", "text": [ "TBP-2" ], "offsets": [ [ 1057, 1062 ] ], "normalized": [] }, { "id": "PMID-16314839_T23", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1108, 1112 ] ], "normalized": [] }, { "id": "PMID-16314839_T24", "type": "Protein", "text": [ "TBP-2" ], "offsets": [ [ 1167, 1172 ] ], "normalized": [] }, { "id": "PMID-16314839_T25", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1176, 1180 ] ], "normalized": [] }, { "id": "PMID-16314839_T26", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1262, 1266 ] ], "normalized": [] }, { "id": "PMID-16314839_T27", "type": "Protein", "text": [ "TBP-2" ], "offsets": [ [ 1281, 1286 ] ], "normalized": [] }, { "id": "PMID-16314839_T28", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1298, 1302 ] ], "normalized": [] }, { "id": "PMID-16314839_T29", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1350, 1354 ] ], "normalized": [] }, { "id": "PMID-16314839_T30", "type": "Protein", "text": [ "TBP-2" ], "offsets": [ [ 1413, 1418 ] ], "normalized": [] }, { "id": "PMID-16314839_T31", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1463, 1467 ] ], "normalized": [] }, { "id": "PMID-16314839_T32", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1498, 1502 ] ], "normalized": [] }, { "id": "PMID-16314839_T33", "type": "Entity", "text": [ "CpGs" ], "offsets": [ [ 612, 616 ] ], "normalized": [] } ]

[ { "id": "PMID-16314839_E1", "type": "DNA_methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 639, 649 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16314839_T11" }, { "role": "Site", "ref_id": "PMID-16314839_T33" } ] }, { "id": "PMID-16314839_E2", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 806, 817 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16314839_T15" }, { "role": "Contextgene", "ref_id": "PMID-16314839_T17" } ] }, { "id": "PMID-16314839_E3", "type": "DNA_methylation", "trigger": { "text": [ "DNA methylation" ], "offsets": [ [ 891, 906 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16314839_T17" } ] }, { "id": "PMID-16314839_E4", "type": "Deacetylation", "trigger": { "text": [ "deacetylation" ], "offsets": [ [ 919, 932 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16314839_T18" }, { "role": "Contextgene", "ref_id": "PMID-16314839_T17" } ] } ]

[ { "id": "PMID-16314839_1", "entity_ids": [ "PMID-16314839_T3", "PMID-16314839_T4" ] }, { "id": "PMID-16314839_2", "entity_ids": [ "PMID-16314839_T6", "PMID-16314839_T7" ] } ]

[]

[ { "id": "PMID-16364251__text", "type": "abstract", "text": [ "Transcriptional silencing of EphB6 receptor tyrosine kinase in invasive breast carcinoma cells and detection of methylated promoter by methylation specific PCR. \nThe receptor tyrosine kinase EphB6 is expressed at reasonable levels in normal breast cells. It shows decreased abundance in non-invasive breast carcinoma cells and is transcriptionally silenced in invasive breast carcinoma cells. We have characterized EphB6 promoter and correlated the expression of EphB6 transcript to differential methylation of the promoter region. The demethylation of promoter sequence in vivo by growth in media containing 5-aza-2'-deoxycytidine restores the expression of EphB6 to normal levels in breast carcinoma cells, and the ability of the promoter to initiate transcription of a reporter gene is lost after methylation of the promoter sequence. The promoter region has binding sites for various factors such as SP1 and p300. The specific methylation of CpG dinucleotides has allowed us to design primers that can selectively amplify the methylated promoter and thus facilitate identification of normal, non-invasive, and invasive breast cells. The potential significance of EphB6 to serve as a diagnostic and prognostic indicator is discussed.\n" ], "offsets": [ [ 0, 1237 ] ] } ]

[ { "id": "PMID-16364251_T1", "type": "Protein", "text": [ "EphB6" ], "offsets": [ [ 29, 34 ] ], "normalized": [] }, { "id": "PMID-16364251_T2", "type": "Protein", "text": [ "EphB6" ], "offsets": [ [ 191, 196 ] ], "normalized": [] }, { "id": "PMID-16364251_T3", "type": "Protein", "text": [ "EphB6" ], "offsets": [ [ 415, 420 ] ], "normalized": [] }, { "id": "PMID-16364251_T4", "type": "Protein", "text": [ "EphB6" ], "offsets": [ [ 463, 468 ] ], "normalized": [] }, { "id": "PMID-16364251_T5", "type": "Protein", "text": [ "EphB6" ], "offsets": [ [ 659, 664 ] ], "normalized": [] }, { "id": "PMID-16364251_T6", "type": "Protein", "text": [ "SP1" ], "offsets": [ [ 904, 907 ] ], "normalized": [] }, { "id": "PMID-16364251_T7", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 912, 916 ] ], "normalized": [] }, { "id": "PMID-16364251_T8", "type": "Protein", "text": [ "EphB6" ], "offsets": [ [ 1167, 1172 ] ], "normalized": [] }, { "id": "PMID-16364251_T10", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 123, 131 ] ], "normalized": [] }, { "id": "PMID-16364251_T12", "type": "Entity", "text": [ "promoter region" ], "offsets": [ [ 515, 530 ] ], "normalized": [] }, { "id": "PMID-16364251_T14", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 553, 561 ] ], "normalized": [] }, { "id": "PMID-16364251_T16", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 819, 827 ] ], "normalized": [] }, { "id": "PMID-16364251_T18", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1041, 1049 ] ], "normalized": [] } ]

[ { "id": "PMID-16364251_E1", "type": "DNA_methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 112, 122 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16364251_T1" }, { "role": "Site", "ref_id": "PMID-16364251_T10" } ] }, { "id": "PMID-16364251_E2", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 496, 507 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16364251_T3" }, { "role": "Site", "ref_id": "PMID-16364251_T12" } ] }, { "id": "PMID-16364251_E3", "type": "DNA_demethylation", "trigger": { "text": [ "demethylation" ], "offsets": [ [ 536, 549 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16364251_T5" }, { "role": "Site", "ref_id": "PMID-16364251_T14" } ] }, { "id": "PMID-16364251_E4", "type": "DNA_methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 800, 811 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16364251_T5" }, { "role": "Site", "ref_id": "PMID-16364251_T16" } ] }, { "id": "PMID-16364251_E5", "type": "DNA_methylation", "trigger": { "text": [ "methylated" ], "offsets": [ [ 1030, 1040 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16364251_T5" }, { "role": "Site", "ref_id": "PMID-16364251_T18" } ] } ]

[]

[]

[ { "id": "PMID-16379001__text", "type": "abstract", "text": [ "Consistent patterns of change during the divergence of human immunodeficiency virus type 1 envelope from that of the inoculated virus in simian/human immunodeficiency virus-infected macaques. \nWe have analyzed changes to proviral Env gp120 sequences and the development of neutralizing antibodies (NAbs) during 1 year of simian/human immunodeficiency virus SHIV-89.6P infection in 11 Macaca nemestrina macaques. Seven macaques had significant env divergence from that of the inoculum, and macaques with greater divergence had higher titers of homologous NAbs. Substitutions in sequons encoding potential N-linked glycosylation sites (PNGs) were among the first to be established, although overall the total number of sequons did not increase significantly. The majority (19 of 23) of PNGs present in the inoculum were conserved in the sequences from all macaques. Statistically significant variations in PNGs occurred in multiple macaques within constrained regions we term \"hot spots,\" resulting in the selection of sequences more similar to the B consensus. These included additions on V1, the N-terminal side of V4, and the outer region of C2. Complex mutational patterns resulted in convergent PNG shifts in V2 and V5. Charge changes in Env V1V2, resulting in a net acidic charge, and a proline addition in V5 occurred in several macaques. Molecular modeling of the 89.6P sequence showed that the conserved glycans lie on the silent face of Env and that many are proximal to disulfide bonds, while PNG additions and shifts are proximal to the CD4 binding site. Nonsynonymous-to-synonymous substitution ratios suggest that these changes result from selective pressure. This longitudinal and cross-sectional study of mutations in human immunodeficiency virus (HIV) env in the SHIV background provides evidence that there are more constraints on the configuration of the glycan shield than were previously appreciated.\n" ], "offsets": [ [ 0, 1920 ] ] } ]

[ { "id": "PMID-16379001_T1", "type": "Protein", "text": [ "Env" ], "offsets": [ [ 230, 233 ] ], "normalized": [] }, { "id": "PMID-16379001_T2", "type": "Protein", "text": [ "gp120" ], "offsets": [ [ 234, 239 ] ], "normalized": [] }, { "id": "PMID-16379001_T3", "type": "Protein", "text": [ "env" ], "offsets": [ [ 443, 446 ] ], "normalized": [] }, { "id": "PMID-16379001_T4", "type": "Protein", "text": [ "Env" ], "offsets": [ [ 1241, 1244 ] ], "normalized": [] }, { "id": "PMID-16379001_T5", "type": "Protein", "text": [ "Env" ], "offsets": [ [ 1445, 1448 ] ], "normalized": [] }, { "id": "PMID-16379001_T6", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1547, 1550 ] ], "normalized": [] }, { "id": "PMID-16379001_T7", "type": "Protein", "text": [ "env" ], "offsets": [ [ 1767, 1770 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-16379001_1", "entity_ids": [ "PMID-16379001_T1", "PMID-16379001_T2" ] } ]

[]

[ { "id": "PMID-16412408__text", "type": "abstract", "text": [ "Patients with congenital hypothyroidism demonstrate different altered expression of plasma fibrinogen and haptoglobin polypeptide chains. \nOBJECTIVES: To compare the plasma protein profiles of treated and untreated congenital hypothyroidism (CH) patients with those of normal control infants. DESIGN AND METHODS: Plasma samples were subjected to two-dimensional gel electrophoresis and silver staining or lectin detection. Resolved protein spots were analyzed by using computerized densitometry software. RESULTS: The significant enhanced expression of the fibrinogen gamma-chain and reduced expression of haptoglobin beta-chain were demonstrated in the profiles of untreated CH patients using both silver staining and lectin detection methods. Lectin detection resolved only a single cluster of the haptoglobin beta-chain for the untreated patients, in contrast to five isoform clusters detected in the controls' and treated CH patients' profiles. CONCLUSIONS: Plasma from untreated CH patients demonstrated different altered expression of fibrinogen and haptoglobin polypeptide chains, which was normalized when patients were treated. Our data also suggest differences in structures of the N-glycans of haptoglobin beta-chain of the untreated CH patients.\n" ], "offsets": [ [ 0, 1258 ] ] } ]

[ { "id": "PMID-16412408_T1", "type": "Protein", "text": [ "haptoglobin" ], "offsets": [ [ 106, 117 ] ], "normalized": [] }, { "id": "PMID-16412408_T2", "type": "Protein", "text": [ "fibrinogen gamma-chain" ], "offsets": [ [ 557, 579 ] ], "normalized": [] }, { "id": "PMID-16412408_T3", "type": "Protein", "text": [ "haptoglobin beta-chain" ], "offsets": [ [ 606, 628 ] ], "normalized": [] }, { "id": "PMID-16412408_T4", "type": "Protein", "text": [ "haptoglobin beta-chain" ], "offsets": [ [ 800, 822 ] ], "normalized": [] }, { "id": "PMID-16412408_T5", "type": "Protein", "text": [ "haptoglobin" ], "offsets": [ [ 1056, 1067 ] ], "normalized": [] }, { "id": "PMID-16412408_T6", "type": "Protein", "text": [ "haptoglobin beta-chain" ], "offsets": [ [ 1205, 1227 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "PMID-16460006__text", "type": "abstract", "text": [ "Chromatin compaction at the mononucleosome level. \nUsing a previously described FRET technique, we measured the distance between the ends of DNA fragments on which nucleosomes were reconstituted from recombinant and native histones. This distance was analyzed in its dependence on the DNA fragment length, concentration of mono- and divalent counterions, presence of linker histone H1, and histone modifications. We found that the linker DNA arms do not cross under all conditions studied but diverge slightly as they leave the histone core surface. Histone H1 leads to a global approach of the linker DNA arms, confirming the notion of a \"stem structure\". Increasing salt concentration also leads to an approach of the linker DNAs. To study the effect of acetylation, we compared chemically acetylated recombinant histones with histones prepared from HeLa cells, characterizing the sites of acetylation by mass spectroscopy. Nucleosomes from chemically acetylated histones have few modifications in the core domain and form nucleosomes normally. Acetylating all histones or selectively only H3 causes an opening of the nucleosome structure, indicated by the larger distances between the linker DNA ends. Selective acetylation of H4 distances the linker ends for short fragments but causes them to approach each other for fragments longer than 180 bp.\n" ], "offsets": [ [ 0, 1352 ] ] } ]

[ { "id": "PMID-16460006_T1", "type": "Protein", "text": [ "histone H1" ], "offsets": [ [ 374, 384 ] ], "normalized": [] }, { "id": "PMID-16460006_T2", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 390, 397 ] ], "normalized": [] }, { "id": "PMID-16460006_T3", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 528, 535 ] ], "normalized": [] }, { "id": "PMID-16460006_T4", "type": "Protein", "text": [ "Histone H1" ], "offsets": [ [ 550, 560 ] ], "normalized": [] }, { "id": "PMID-16460006_T5", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 815, 823 ] ], "normalized": [] }, { "id": "PMID-16460006_T6", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 829, 837 ] ], "normalized": [] }, { "id": "PMID-16460006_T7", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 965, 973 ] ], "normalized": [] }, { "id": "PMID-16460006_T8", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 1063, 1071 ] ], "normalized": [] }, { "id": "PMID-16460006_T9", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1092, 1094 ] ], "normalized": [] }, { "id": "PMID-16460006_T10", "type": "Protein", "text": [ "H4" ], "offsets": [ [ 1230, 1232 ] ], "normalized": [] } ]

[ { "id": "PMID-16460006_E1", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 792, 802 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16460006_T5" } ] }, { "id": "PMID-16460006_E2", "type": "Acetylation", "trigger": { "text": [ "acetylated" ], "offsets": [ [ 954, 964 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16460006_T7" } ] }, { "id": "PMID-16460006_E3", "type": "Acetylation", "trigger": { "text": [ "Acetylating" ], "offsets": [ [ 1047, 1058 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16460006_T8" } ] }, { "id": "PMID-16460006_E4", "type": "Acetylation", "trigger": { "text": [ "Acetylating" ], "offsets": [ [ 1047, 1058 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16460006_T9" } ] }, { "id": "PMID-16460006_E5", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 1215, 1226 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16460006_T10" } ] } ]

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[ { "id": "PMID-16465382__text", "type": "abstract", "text": [ "Histone deacetylase inhibitors induce cell death and enhance the susceptibility to ionizing radiation, etoposide, and TRAIL in medulloblastoma cells. \nHistone deacetylase inhibitors (HDIs) are a promising new class of antineoplastic agents with the ability to induce apoptosis and growth arrest of cancer cells. In addition, HDIs have been suggested to enhance the anticancer efficacy of other therapeutic regimens, such as ionizing radiation (IR) or chemotherapy. The objective of this study was to evaluate the activity of HDIs against medulloblastoma cells when applied either as single agents or in combination with IR, cytostatics, or TRAIL. The HDIs, suberoyl anilide hydroxamic acid (SAHA), sodium butyrate, and trichostatin A, were examined for their effects on the medulloblastoma cell lines, DAOY and UW228-2. We found that treatment with HDIs induced the dissipation of mitochondrial membrane potential, activation of caspase-9 and -3 and, consequently, apoptotic cell death. Moreover, all three HDIs significantly enhanced the cytotoxic effects of IR in DAOY cells. Likewise, treatment with SAHA markedly augmented the cytotoxicity of etoposide, while it had no effect on vincristine-mediated cell death. HDIs also potently increased the killing efficiency of TRAIL. TRAIL-induced, but not SAHA-induced, cell killing could be prevented by the caspase-8 inhibitor, z-IEDT-fmk. We conclude that HDIs may be useful for the treatment of medulloblastoma as monotherapy and particularly when given in combination with IR, appropriate cytostatics, or TRAIL.\n" ], "offsets": [ [ 0, 1563 ] ] } ]

[ { "id": "PMID-16465382_T1", "type": "Protein", "text": [ "Histone" ], "offsets": [ [ 0, 7 ] ], "normalized": [] }, { "id": "PMID-16465382_T2", "type": "Protein", "text": [ "Histone" ], "offsets": [ [ 151, 158 ] ], "normalized": [] }, { "id": "PMID-16465382_T3", "type": "Protein", "text": [ "caspase-9" ], "offsets": [ [ 929, 938 ] ], "normalized": [] }, { "id": "PMID-16465382_T4", "type": "Protein", "text": [ "-3" ], "offsets": [ [ 943, 945 ] ], "normalized": [] }, { "id": "PMID-16465382_T5", "type": "Protein", "text": [ "caspase-8" ], "offsets": [ [ 1355, 1364 ] ], "normalized": [] } ]

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[ { "id": "PMID-16497731__text", "type": "abstract", "text": [ "Adiponectin multimerization is dependent on conserved lysines in the collagenous domain: evidence for regulation of multimerization by alterations in posttranslational modifications. \nAdiponectin is a secreted, multimeric protein with insulin-sensitizing, antiatherogenic, and antiinflammatory properties. Serum adiponectin consists of trimer, hexamer, and larger high-molecular-weight (HMW) multimers, and these HMW multimers appear to be the more bioactive forms. Multimer composition of adiponectin appears to be regulated; however, the molecular mechanisms involved are unknown. We hypothesize that regulation of adiponectin multimerization and secretion occurs via changes in posttranslational modifications (PTMs). Although a structural role for intertrimer disulfide bonds in the formation of hexamers and HMW multimers is established, the role of other PTMs is unknown. PTMs identified in murine and bovine adiponectin include hydroxylation of multiple conserved proline and lysine residues and glycosylation of hydroxylysines. By mass spectrometry, we confirmed the presence of these PTMs in human adiponectin and identified three additional hydroxylations on Pro71, Pro76, and Pro95. We also investigated the role of the five modified lysines in multimer formation and secretion of recombinant human adiponectin expressed in mammalian cell lines. Mutation of modified lysines in the collagenous domain prevented formation of HMW multimers, whereas a pharmacological inhibitor of prolyl- and lysyl-hydroxylases, 2,2'-dipyridyl, inhibited formation of hexamers and HMW multimers. Bacterially expressed human adiponectin displayed a complete lack of differentially modified isoforms and failed to form bona fide trimers and larger multimers. Finally, glucose-induced increases in HMW multimer production from human adipose explants correlated with changes in the two-dimensional electrophoresis profile of adiponectin isoforms. Collectively, these data suggest that adiponectin multimer composition is affected by changes in PTM in response to physiological factors.\n" ], "offsets": [ [ 0, 2074 ] ] } ]

[ { "id": "PMID-16497731_T1", "type": "Protein", "text": [ "Adiponectin" ], "offsets": [ [ 0, 11 ] ], "normalized": [] }, { "id": "PMID-16497731_T2", "type": "Protein", "text": [ "Adiponectin" ], "offsets": [ [ 184, 195 ] ], "normalized": [] }, { "id": "PMID-16497731_T3", "type": "Protein", "text": [ "insulin" ], "offsets": [ [ 235, 242 ] ], "normalized": [] }, { "id": "PMID-16497731_T4", "type": "Protein", "text": [ "adiponectin" ], "offsets": [ [ 312, 323 ] ], "normalized": [] }, { "id": "PMID-16497731_T5", "type": "Protein", "text": [ "adiponectin" ], "offsets": [ [ 490, 501 ] ], "normalized": [] }, { "id": "PMID-16497731_T6", "type": "Protein", "text": [ "adiponectin" ], "offsets": [ [ 617, 628 ] ], "normalized": [] }, { "id": "PMID-16497731_T7", "type": "Protein", "text": [ "adiponectin" ], "offsets": [ [ 915, 926 ] ], "normalized": [] }, { "id": "PMID-16497731_T8", "type": "Protein", "text": [ "adiponectin" ], "offsets": [ [ 1107, 1118 ] ], "normalized": [] }, { "id": "PMID-16497731_T9", "type": "Protein", "text": [ "adiponectin" ], "offsets": [ [ 1310, 1321 ] ], "normalized": [] }, { "id": "PMID-16497731_T10", "type": "Protein", "text": [ "adiponectin" ], "offsets": [ [ 1616, 1627 ] ], "normalized": [] }, { "id": "PMID-16497731_T11", "type": "Protein", "text": [ "adiponectin" ], "offsets": [ [ 1913, 1924 ] ], "normalized": [] }, { "id": "PMID-16497731_T12", "type": "Protein", "text": [ "adiponectin" ], "offsets": [ [ 1973, 1984 ] ], "normalized": [] }, { "id": "PMID-16497731_T14", "type": "Entity", "text": [ "proline" ], "offsets": [ [ 971, 978 ] ], "normalized": [] }, { "id": "PMID-16497731_T15", "type": "Entity", "text": [ "lysine residues" ], "offsets": [ [ 983, 998 ] ], "normalized": [] }, { "id": "PMID-16497731_T17", "type": "Entity", "text": [ "hydroxylysines" ], "offsets": [ [ 1020, 1034 ] ], "normalized": [] }, { "id": "PMID-16497731_T19", "type": "Entity", "text": [ "Pro71" ], "offsets": [ [ 1169, 1174 ] ], "normalized": [] }, { "id": "PMID-16497731_T20", "type": "Entity", "text": [ "Pro76" ], "offsets": [ [ 1176, 1181 ] ], "normalized": [] }, { "id": "PMID-16497731_T21", "type": "Entity", "text": [ "Pro95" ], "offsets": [ [ 1187, 1192 ] ], "normalized": [] } ]

[ { "id": "PMID-16497731_E1", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 935, 948 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16497731_T7" }, { "role": "Site", "ref_id": "PMID-16497731_T14" } ] }, { "id": "PMID-16497731_E2", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylation" ], "offsets": [ [ 935, 948 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16497731_T7" }, { "role": "Site", "ref_id": "PMID-16497731_T15" } ] }, { "id": "PMID-16497731_E3", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 1003, 1016 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16497731_T7" }, { "role": "Site", "ref_id": "PMID-16497731_T17" } ] }, { "id": "PMID-16497731_E4", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylations" ], "offsets": [ [ 1151, 1165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16497731_T8" }, { "role": "Site", "ref_id": "PMID-16497731_T19" } ] }, { "id": "PMID-16497731_E5", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylations" ], "offsets": [ [ 1151, 1165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16497731_T8" }, { "role": "Site", "ref_id": "PMID-16497731_T20" } ] }, { "id": "PMID-16497731_E6", "type": "Hydroxylation", "trigger": { "text": [ "hydroxylations" ], "offsets": [ [ 1151, 1165 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16497731_T8" }, { "role": "Site", "ref_id": "PMID-16497731_T21" } ] } ]

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[]

[ { "id": "PMID-16506098__text", "type": "abstract", "text": [ "Heterochromatin assembly: a new twist on an old model. \nThe organization of eukaryotic genomes requires a harmony between efficient compaction and accessibility. This is achieved through its packaging into chromatin. Chromatin can be subdivided into two general structural and functional compartments: euchromatin and heterochromatin. Euchromatin comprises most of the expressed genome, while heterochromatin participates intimately in the production of structures such as centromeres and telomeres essential for chromosome function. Studies in the fission yeast Schizosaccharomyces pombe have begun to highlight the genetic pathways critical for the assembly and epigenetic maintenance of heterochromatin, including key roles played by the RNAi machinery, H3 lysine 9 methylation and heterochromatin protein 1 (HP1). Recent studies have also identified a novel E3 ubiquitin ligase universally required for H3 K9 methylation. Here we outline these studies and propose several models for the role of this E3 ligase in heterochromatin assembly.\n" ], "offsets": [ [ 0, 1043 ] ] } ]

[ { "id": "PMID-16506098_T1", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 757, 759 ] ], "normalized": [] }, { "id": "PMID-16506098_T2", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 907, 909 ] ], "normalized": [] }, { "id": "PMID-16506098_T3", "type": "Entity", "text": [ "lysine 9" ], "offsets": [ [ 760, 768 ] ], "normalized": [] }, { "id": "PMID-16506098_T5", "type": "Entity", "text": [ "K9" ], "offsets": [ [ 910, 912 ] ], "normalized": [] } ]

[ { "id": "PMID-16506098_E1", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 769, 780 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16506098_T1" }, { "role": "Site", "ref_id": "PMID-16506098_T3" } ] }, { "id": "PMID-16506098_E2", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 913, 924 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16506098_T2" }, { "role": "Site", "ref_id": "PMID-16506098_T5" } ] } ]

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[ { "id": "PMID-16516177__text", "type": "abstract", "text": [ "In vitro sulfation of N-acetyllactosaminide by soluble recombinant human beta-Gal-3'-sulfotransferase. \nMembrane-bound beta-Gal-3'-sulfotransferase (GP3ST) was expressed and used for in vitro sulfation of Tamm-Horsfall glycoprotein. Further, the regioselective transfer of sulfate to an N-acetyllactosamine derivative could be realised with soluble chimeric GP3ST, also in combination with Lac transglycosylation by means of beta-galactosidase. Two alternative straightforward chemical syntheses for the target compound could be elaborated.\n" ], "offsets": [ [ 0, 541 ] ] } ]

[ { "id": "PMID-16516177_T1", "type": "Protein", "text": [ "beta-Gal-3'-sulfotransferase" ], "offsets": [ [ 73, 101 ] ], "normalized": [] }, { "id": "PMID-16516177_T2", "type": "Protein", "text": [ "beta-Gal-3'-sulfotransferase" ], "offsets": [ [ 119, 147 ] ], "normalized": [] }, { "id": "PMID-16516177_T3", "type": "Protein", "text": [ "GP3ST" ], "offsets": [ [ 149, 154 ] ], "normalized": [] }, { "id": "PMID-16516177_T4", "type": "Protein", "text": [ "Tamm-Horsfall glycoprotein" ], "offsets": [ [ 205, 231 ] ], "normalized": [] }, { "id": "PMID-16516177_T5", "type": "Protein", "text": [ "GP3ST" ], "offsets": [ [ 358, 363 ] ], "normalized": [] }, { "id": "PMID-16516177_T6", "type": "Protein", "text": [ "beta-galactosidase" ], "offsets": [ [ 425, 443 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-16516177_1", "entity_ids": [ "PMID-16516177_T2", "PMID-16516177_T3" ] } ]

[]

[ { "id": "PMID-16531626__text", "type": "abstract", "text": [ "Acetylation genotype and phenotype in patients with systemic lupus erythematosus. \nSystemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting various tissues and organs. In the studies on SLE etiopathogenesis, a potential role of genetically determined impairment of xenobiotic metabolism has been emphasized. N-acetyltransferase 2 enzyme (NAT2) exhibits gene polymorphism and the acetylation rate with NAT2 involvement varies from person to person. The study on acetylation phenotype was carried out using isonicotinic acid hydrazide (isoniazid) as a model drug, while NAT2 alleles were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. Among patients with SLE, NAT2*4/NAT2*6 and NAT2*5/NAT2*5 genotypes occurred most frequently, while NAT2*4/NAT2*6 and NAT2*5/NAT2*6 prevailed in the control group. The concordance of 96.8% was achieved between acetylation phenotype and NAT2 genotype in the group of SLE patients studied. Conclusion: Acetylation polymorphism appears not to be an important risk factor in SLE.\n" ], "offsets": [ [ 0, 1085 ] ] } ]

[ { "id": "PMID-16531626_T1", "type": "Protein", "text": [ "N-acetyltransferase 2" ], "offsets": [ [ 328, 349 ] ], "normalized": [] }, { "id": "PMID-16531626_T2", "type": "Protein", "text": [ "NAT2" ], "offsets": [ [ 358, 362 ] ], "normalized": [] }, { "id": "PMID-16531626_T3", "type": "Protein", "text": [ "NAT2" ], "offsets": [ [ 421, 425 ] ], "normalized": [] }, { "id": "PMID-16531626_T4", "type": "Protein", "text": [ "NAT2" ], "offsets": [ [ 588, 592 ] ], "normalized": [] }, { "id": "PMID-16531626_T5", "type": "Protein", "text": [ "NAT2" ], "offsets": [ [ 735, 739 ] ], "normalized": [] }, { "id": "PMID-16531626_T6", "type": "Protein", "text": [ "NAT2" ], "offsets": [ [ 742, 746 ] ], "normalized": [] }, { "id": "PMID-16531626_T7", "type": "Protein", "text": [ "NAT2" ], "offsets": [ [ 753, 757 ] ], "normalized": [] }, { "id": "PMID-16531626_T8", "type": "Protein", "text": [ "NAT2" ], "offsets": [ [ 760, 764 ] ], "normalized": [] }, { "id": "PMID-16531626_T9", "type": "Protein", "text": [ "NAT2" ], "offsets": [ [ 809, 813 ] ], "normalized": [] }, { "id": "PMID-16531626_T10", "type": "Protein", "text": [ "NAT2" ], "offsets": [ [ 816, 820 ] ], "normalized": [] }, { "id": "PMID-16531626_T11", "type": "Protein", "text": [ "NAT2" ], "offsets": [ [ 827, 831 ] ], "normalized": [] }, { "id": "PMID-16531626_T12", "type": "Protein", "text": [ "NAT2" ], "offsets": [ [ 834, 838 ] ], "normalized": [] }, { "id": "PMID-16531626_T13", "type": "Protein", "text": [ "NAT2" ], "offsets": [ [ 945, 949 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-16531626_1", "entity_ids": [ "PMID-16531626_T1", "PMID-16531626_T2" ] } ]

[]

[ { "id": "PMID-16547097__text", "type": "abstract", "text": [ "Nonadditive regulation of FRI and FLC loci mediates flowering-time variation in Arabidopsis allopolyploids. \nAllopolyploidy is formed by combining two or more divergent genomes and occurs throughout the evolutionary history of many plants and some animals. Transcriptome analysis indicates that many genes in various biological pathways, including flowering time, are expressed nonadditively (different from the midparent value). However, the mechanisms for nonadditive gene regulation in a biological pathway are unknown. Natural variation of flowering time is largely controlled by two epistatically acting loci, namely FRIGIDA (FRI) and FLOWERING LOCUS C (FLC). FRI upregulates FLC expression that represses flowering in Arabidopsis. Synthetic Arabidopsis allotetraploids contain two sets of FLC and FRI genes originating from Arabidopsis thaliana and A. arenosa, respectively, and flower late. Inhibition of early flowering is caused by upregulation of A. thaliana FLC (AtFLC) that is trans-activated by A. arenosa FRI (AaFRI). Two duplicate FLCs (AaFLC1 and AaFLC2) originating from A. arenosa are expressed in some allotetraploids but silenced in other lines. The expression variation in the allotetraploids is associated with deletions in the promoter regions and first introns of A. arenosa FLCs. The strong AtFLC and AaFLC loci are maintained in natural Arabidopsis allotetraploids, leading to extremely late flowering. Furthermore, FLC expression correlates positively with histone H3-Lys4 methylation and H3-Lys9 acetylation and negatively with H3-Lys9 methylation, epigenetic marks for gene activation and silencing. We provide evidence for interactive roles of regulatory sequence changes, chromatin modification, and trans-acting effects in natural selection of orthologous FLC loci, which determines the fate of duplicate genes and adaptation of allopolyploids during evolution.\n" ], "offsets": [ [ 0, 1894 ] ] } ]

[ { "id": "PMID-16547097_T1", "type": "Protein", "text": [ "FRI" ], "offsets": [ [ 26, 29 ] ], "normalized": [] }, { "id": "PMID-16547097_T2", "type": "Protein", "text": [ "FRIGIDA" ], "offsets": [ [ 622, 629 ] ], "normalized": [] }, { "id": "PMID-16547097_T3", "type": "Protein", "text": [ "FRI" ], "offsets": [ [ 631, 634 ] ], "normalized": [] }, { "id": "PMID-16547097_T4", "type": "Protein", "text": [ "FLOWERING LOCUS C" ], "offsets": [ [ 640, 657 ] ], "normalized": [] }, { "id": "PMID-16547097_T5", "type": "Protein", "text": [ "FLC" ], "offsets": [ [ 659, 662 ] ], "normalized": [] }, { "id": "PMID-16547097_T6", "type": "Protein", "text": [ "FRI" ], "offsets": [ [ 665, 668 ] ], "normalized": [] }, { "id": "PMID-16547097_T7", "type": "Protein", "text": [ "FLC" ], "offsets": [ [ 681, 684 ] ], "normalized": [] }, { "id": "PMID-16547097_T8", "type": "Protein", "text": [ "FLC" ], "offsets": [ [ 969, 972 ] ], "normalized": [] }, { "id": "PMID-16547097_T9", "type": "Protein", "text": [ "FLC" ], "offsets": [ [ 976, 979 ] ], "normalized": [] }, { "id": "PMID-16547097_T10", "type": "Protein", "text": [ "FRI" ], "offsets": [ [ 1019, 1022 ] ], "normalized": [] }, { "id": "PMID-16547097_T11", "type": "Protein", "text": [ "FRI" ], "offsets": [ [ 1026, 1029 ] ], "normalized": [] }, { "id": "PMID-16547097_T12", "type": "Protein", "text": [ "FLC1" ], "offsets": [ [ 1054, 1058 ] ], "normalized": [] }, { "id": "PMID-16547097_T13", "type": "Protein", "text": [ "FLC2" ], "offsets": [ [ 1065, 1069 ] ], "normalized": [] }, { "id": "PMID-16547097_T14", "type": "Protein", "text": [ "FLC" ], "offsets": [ [ 1318, 1321 ] ], "normalized": [] }, { "id": "PMID-16547097_T15", "type": "Protein", "text": [ "histone H3" ], "offsets": [ [ 1484, 1494 ] ], "normalized": [] }, { "id": "PMID-16547097_T16", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1516, 1518 ] ], "normalized": [] }, { "id": "PMID-16547097_T17", "type": "Protein", "text": [ "H3" ], "offsets": [ [ 1556, 1558 ] ], "normalized": [] }, { "id": "PMID-16547097_T18", "type": "Protein", "text": [ "FLC" ], "offsets": [ [ 1788, 1791 ] ], "normalized": [] }, { "id": "PMID-16547097_T19", "type": "Entity", "text": [ "Lys4" ], "offsets": [ [ 1495, 1499 ] ], "normalized": [] }, { "id": "PMID-16547097_T21", "type": "Entity", "text": [ "Lys9" ], "offsets": [ [ 1519, 1523 ] ], "normalized": [] }, { "id": "PMID-16547097_T23", "type": "Entity", "text": [ "Lys9" ], "offsets": [ [ 1559, 1563 ] ], "normalized": [] } ]

[ { "id": "PMID-16547097_E1", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1500, 1511 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16547097_T15" }, { "role": "Site", "ref_id": "PMID-16547097_T19" } ] }, { "id": "PMID-16547097_E2", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 1524, 1535 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16547097_T16" }, { "role": "Site", "ref_id": "PMID-16547097_T21" } ] }, { "id": "PMID-16547097_E3", "type": "Methylation", "trigger": { "text": [ "methylation" ], "offsets": [ [ 1564, 1575 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16547097_T17" }, { "role": "Site", "ref_id": "PMID-16547097_T23" } ] } ]

[ { "id": "PMID-16547097_1", "entity_ids": [ "PMID-16547097_T2", "PMID-16547097_T3" ] }, { "id": "PMID-16547097_2", "entity_ids": [ "PMID-16547097_T4", "PMID-16547097_T5" ] } ]

[]

[ { "id": "PMID-1655342__text", "type": "abstract", "text": [ "Evidence for heterogeneity of glycosylation of human renin obtained by using lectins. \n1. In this study, the carbohydrate structure of pure human renin was examined by using various lectins. 2. Pure renin could be separated into three forms by concanavalin A chromatography, a concanavalin A-unbound form, a loosely bound form and a tightly bound form, termed renins A, B and C, respectively. Renins A, B and C accounted for 3, 13 and 84%, respectively, of the purified renin. These forms were all present in individual human plasma and the relative proportions in plasma were 27 +/- 3, 33 +/- 4 and 39 +/- 5% (means +/- SEM) for renins A, B and C, respectively (n = 5). 3. Each form, electroblotted on to the nitrocellulose sheet after gel electrophoresis, was incubated with five peroxidase-labelled lectins, lentil lectin, erythroagglutinating phytohaemagglutinin, wheat-germ agglutinin, Ricinus communis agglutinin and peanut agglutinin. The protein was stained with 4-chloro-1-naphthol. 4. The staining pattern obtained with these lectins was significantly different among the three forms of human renin, confirming that they have different carbohydrate structures. Furthermore, the positive staining of human renin with erythroagglutinating phytohaemagglutinin, wheat-germ agglutinin and Ricinus communis agglutinin was in contrast with the lack of binding of rat renin to these lectins. 5. These results indicate the renal secretion of differently glycosylated multiple forms of human renin. The carbohydrate structure of human renin appears to differ from that of rat renin.\n" ], "offsets": [ [ 0, 1584 ] ] } ]

[ { "id": "PMID-1655342_T1", "type": "Protein", "text": [ "renin" ], "offsets": [ [ 53, 58 ] ], "normalized": [] }, { "id": "PMID-1655342_T2", "type": "Protein", "text": [ "renin" ], "offsets": [ [ 147, 152 ] ], "normalized": [] }, { "id": "PMID-1655342_T3", "type": "Protein", "text": [ "renin" ], "offsets": [ [ 200, 205 ] ], "normalized": [] }, { "id": "PMID-1655342_T4", "type": "Protein", "text": [ "concanavalin A" ], "offsets": [ [ 245, 259 ] ], "normalized": [] }, { "id": "PMID-1655342_T5", "type": "Protein", "text": [ "concanavalin A" ], "offsets": [ [ 278, 292 ] ], "normalized": [] }, { "id": "PMID-1655342_T6", "type": "Protein", "text": [ "renins" ], "offsets": [ [ 361, 367 ] ], "normalized": [] }, { "id": "PMID-1655342_T7", "type": "Protein", "text": [ "renin" ], "offsets": [ [ 471, 476 ] ], "normalized": [] }, { "id": "PMID-1655342_T8", "type": "Protein", "text": [ "lectin" ], "offsets": [ [ 819, 825 ] ], "normalized": [] }, { "id": "PMID-1655342_T9", "type": "Protein", "text": [ "erythroagglutinating phytohaemagglutinin" ], "offsets": [ [ 827, 867 ] ], "normalized": [] }, { "id": "PMID-1655342_T10", "type": "Protein", "text": [ "agglutinin" ], "offsets": [ [ 909, 919 ] ], "normalized": [] }, { "id": "PMID-1655342_T11", "type": "Protein", "text": [ "agglutinin" ], "offsets": [ [ 931, 941 ] ], "normalized": [] }, { "id": "PMID-1655342_T12", "type": "Protein", "text": [ "renin" ], "offsets": [ [ 1104, 1109 ] ], "normalized": [] }, { "id": "PMID-1655342_T13", "type": "Protein", "text": [ "renin" ], "offsets": [ [ 1216, 1221 ] ], "normalized": [] }, { "id": "PMID-1655342_T14", "type": "Protein", "text": [ "erythroagglutinating phytohaemagglutinin" ], "offsets": [ [ 1227, 1267 ] ], "normalized": [] }, { "id": "PMID-1655342_T15", "type": "Protein", "text": [ "agglutinin" ], "offsets": [ [ 1312, 1322 ] ], "normalized": [] }, { "id": "PMID-1655342_T16", "type": "Protein", "text": [ "renin" ], "offsets": [ [ 1371, 1376 ] ], "normalized": [] }, { "id": "PMID-1655342_T17", "type": "Protein", "text": [ "renin" ], "offsets": [ [ 1493, 1498 ] ], "normalized": [] }, { "id": "PMID-1655342_T18", "type": "Protein", "text": [ "renin" ], "offsets": [ [ 1536, 1541 ] ], "normalized": [] }, { "id": "PMID-1655342_T19", "type": "Protein", "text": [ "renin" ], "offsets": [ [ 1577, 1582 ] ], "normalized": [] } ]

[ { "id": "PMID-1655342_E1", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 30, 43 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655342_T1" } ] }, { "id": "PMID-1655342_E2", "type": "Glycosylation", "trigger": { "text": [ "glycosylated" ], "offsets": [ [ 1456, 1468 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-1655342_T17" } ] } ]

[]

[]

[ { "id": "PMID-1656972__text", "type": "abstract", "text": [ "Glycosylation of high-affinity thrombin receptors appears necessary for thrombin binding. \nMonosaccharide binding competition, lectin affinity chromatography, and glycosylation inhibitors have been used to determine if glycosylation plays a role in thrombin-receptor interactions. Mannose appeared to specifically inhibit thrombin binding to mouse embryo (ME) and hamster fibroblasts. Concanavalin A bound to antibody-purified receptor fractions, and was used as an affinity ligand to purify receptor fractions that retained thrombin binding activity. Cells treated with tunicamycin (6.25 ng/ml) for 24 h lost approximately 35% of their high-affinity thrombin binding sites, yet binding of receptor monoclonal antibody TR-9 was not affected, indicating that the receptor was present in the membrane, but unable to bind thrombin. Thus thrombin receptor glycosylation may be directly involved in thrombin binding.\n" ], "offsets": [ [ 0, 912 ] ] } ]

[ { "id": "PMID-1656972_T1", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 31, 39 ] ], "normalized": [] }, { "id": "PMID-1656972_T2", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 72, 80 ] ], "normalized": [] }, { "id": "PMID-1656972_T3", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 249, 257 ] ], "normalized": [] }, { "id": "PMID-1656972_T4", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 322, 330 ] ], "normalized": [] }, { "id": "PMID-1656972_T5", "type": "Protein", "text": [ "Concanavalin A" ], "offsets": [ [ 385, 399 ] ], "normalized": [] }, { "id": "PMID-1656972_T6", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 525, 533 ] ], "normalized": [] }, { "id": "PMID-1656972_T7", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 651, 659 ] ], "normalized": [] }, { "id": "PMID-1656972_T8", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 819, 827 ] ], "normalized": [] }, { "id": "PMID-1656972_T9", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 834, 842 ] ], "normalized": [] }, { "id": "PMID-1656972_T10", "type": "Protein", "text": [ "thrombin" ], "offsets": [ [ 894, 902 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-16571791__text", "type": "abstract", "text": [ "Functional mapping of the nucleoprotein of Ebola virus. \nAt 739 amino acids, the nucleoprotein (NP) of Ebola virus is the largest nucleoprotein of the nonsegmented negative-stranded RNA viruses, and like the NPs of other viruses, it plays a central role in virus replication. Huang et al. (Y. Huang, L. Xu, Y. Sun, and G. J. Nabel, Mol. Cell 10:307-316, 2002) previously demonstrated that NP, together with the minor matrix protein VP24 and polymerase cofactor VP35, is necessary and sufficient for the formation of nucleocapsid-like structures that are morphologically indistinguishable from those seen in Ebola virus-infected cells. They further showed that NP is O glycosylated and sialylated and that these modifications are important for interaction between NP and VP35. However, little is known about the structure-function relationship of Ebola virus NP. Here, we examined the glycosylation of Ebola virus NP and further investigated its properties by generating deletion mutants to define the region(s) involved in NP-NP interaction (self-assembly), in the formation of nucleocapsid-like structures, and in the replication of the viral genome. We were unable to identify the types of glycosylation and sialylation, although we did confirm that Ebola virus NP was glycosylated. We also determined that the region from amino acids 1 to 450 is important for NP-NP interaction (self-assembly). We further demonstrated that these amino-terminal 450 residues and the following 150 residues are required for the formation of nucleocapsid-like structures and for viral genome replication. These data advance our understanding of the functional region(s) of Ebola virus NP, which in turn should improve our knowledge of the Ebola virus life cycle and its extreme pathogenicity.\n" ], "offsets": [ [ 0, 1777 ] ] } ]

[ { "id": "PMID-16571791_T1", "type": "Protein", "text": [ "nucleoprotein" ], "offsets": [ [ 81, 94 ] ], "normalized": [] }, { "id": "PMID-16571791_T2", "type": "Protein", "text": [ "NP" ], "offsets": [ [ 96, 98 ] ], "normalized": [] }, { "id": "PMID-16571791_T3", "type": "Protein", "text": [ "NP" ], "offsets": [ [ 389, 391 ] ], "normalized": [] }, { "id": "PMID-16571791_T4", "type": "Protein", "text": [ "VP24" ], "offsets": [ [ 432, 436 ] ], "normalized": [] }, { "id": "PMID-16571791_T5", "type": "Protein", "text": [ "VP35" ], "offsets": [ [ 461, 465 ] ], "normalized": [] }, { "id": "PMID-16571791_T6", "type": "Protein", "text": [ "NP" ], "offsets": [ [ 660, 662 ] ], "normalized": [] }, { "id": "PMID-16571791_T7", "type": "Protein", "text": [ "NP" ], "offsets": [ [ 763, 765 ] ], "normalized": [] }, { "id": "PMID-16571791_T8", "type": "Protein", "text": [ "VP35" ], "offsets": [ [ 770, 774 ] ], "normalized": [] }, { "id": "PMID-16571791_T9", "type": "Protein", "text": [ "NP" ], "offsets": [ [ 858, 860 ] ], "normalized": [] }, { "id": "PMID-16571791_T10", "type": "Protein", "text": [ "NP" ], "offsets": [ [ 913, 915 ] ], "normalized": [] }, { "id": "PMID-16571791_T11", "type": "Protein", "text": [ "NP" ], "offsets": [ [ 1023, 1025 ] ], "normalized": [] }, { "id": "PMID-16571791_T12", "type": "Protein", "text": [ "NP" ], "offsets": [ [ 1026, 1028 ] ], "normalized": [] }, { "id": "PMID-16571791_T13", "type": "Protein", "text": [ "NP" ], "offsets": [ [ 1264, 1266 ] ], "normalized": [] }, { "id": "PMID-16571791_T14", "type": "Protein", "text": [ "NP" ], "offsets": [ [ 1363, 1365 ] ], "normalized": [] }, { "id": "PMID-16571791_T15", "type": "Protein", "text": [ "NP" ], "offsets": [ [ 1366, 1368 ] ], "normalized": [] }, { "id": "PMID-16571791_T16", "type": "Protein", "text": [ "NP" ], "offsets": [ [ 1669, 1671 ] ], "normalized": [] } ]

[ { "id": "PMID-16571791_E1", "type": "Glycosylation", "trigger": { "text": [ "O glycosylated" ], "offsets": [ [ 666, 680 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16571791_T6" } ] }, { "id": "PMID-16571791_E2", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 884, 897 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16571791_T10" } ] }, { "id": "PMID-16571791_E3", "type": "Glycosylation", "trigger": { "text": [ "glycosylated" ], "offsets": [ [ 1271, 1283 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16571791_T13" } ] } ]

[ { "id": "PMID-16571791_1", "entity_ids": [ "PMID-16571791_T1", "PMID-16571791_T2" ] } ]

[]

[ { "id": "PMID-16583246__text", "type": "abstract", "text": [ "Defective glycosylation of decorin and biglycan, altered collagen structure, and abnormal phenotype of the skin fibroblasts of an Ehlers-Danlos syndrome patient carrying the novel Arg270Cys substitution in galactosyltransferase I (beta4GalT-7). \nThe Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue disorders affecting skin and joint function. Molecular defects in extracellular matrix proteins, including collagen (type I, III, and V) and tenascin X are associated with different forms of EDS. Compound heterozygous mutations in the B4GALT7 gene, resulting in aberrant glycosylation of the dermatan sulfate proteoglycan decorin, had been described in a single patient affected with the progeroid form of EDS. We have studied the molecular phenotype of decorin, biglycan, and collagen type I containing fibrils in skin fibroblasts of a patient carrying the novel homozygous C808T point mutation in the B4GALT7 gene, which causes an Arg270Cys substitution in beta4GalT-7. Compared to control fibroblasts, galactosyltransferase activity in beta4GalT-7(Arg270Cys) cells was approximately three times reduced over a temperature range of 25-41 degrees C. Pulse-chase experiments and confocal microscopy demonstrated that synthesis and secretion of decorin were normal in beta4GalT-7(Arg270Cys) cells. However, about 50% of decorin were synthesized as a protein core in addition to its proteoglycan form. Biglycan was found in a monoglycanated form in addition to its mature form. Glycosaminoglycan chains were of the dermatan/chondroitin sulfate type both in beta4GalT-7(Arg270Cys) and control cells, and epimerization was reduced for decorin and biglycan. Compared to control cells, beta4GalT-7(Arg270Cys) cells showed altered, highly spread or stretched phenotypes and decreased proliferation rates. At the ultrastructural level, an intracellular accumulation of multiple secondary lysosomes and degenerative vacuoles was seen in beta4GalT-7(Arg270Cys) cells. Furthermore, the collagen suprastructures were altered in the beta4GalT-7(Arg270Cys) cells. The reduced beta4GalT-7 activity resulting in defective glycosylation of decorin and biglycan may be responsible for the complex molecular pathology in beta4GalT-7 deficient EDS patients, given the role of these proteoglycans in bone formation, collagen fibrillogenesis, and skeletal muscle development.\n" ], "offsets": [ [ 0, 2379 ] ] } ]

[ { "id": "PMID-16583246_T1", "type": "Protein", "text": [ "decorin" ], "offsets": [ [ 27, 34 ] ], "normalized": [] }, { "id": "PMID-16583246_T2", "type": "Protein", "text": [ "biglycan" ], "offsets": [ [ 39, 47 ] ], "normalized": [] }, { "id": "PMID-16583246_T3", "type": "Protein", "text": [ "beta4GalT-7" ], "offsets": [ [ 231, 242 ] ], "normalized": [] }, { "id": "PMID-16583246_T4", "type": "Protein", "text": [ "tenascin X" ], "offsets": [ [ 466, 476 ] ], "normalized": [] }, { "id": "PMID-16583246_T5", "type": "Protein", "text": [ "B4GALT7" ], "offsets": [ [ 560, 567 ] ], "normalized": [] }, { "id": "PMID-16583246_T6", "type": "Protein", "text": [ "decorin" ], "offsets": [ [ 647, 654 ] ], "normalized": [] }, { "id": "PMID-16583246_T7", "type": "Protein", "text": [ "decorin" ], "offsets": [ [ 779, 786 ] ], "normalized": [] }, { "id": "PMID-16583246_T8", "type": "Protein", "text": [ "biglycan" ], "offsets": [ [ 788, 796 ] ], "normalized": [] }, { "id": "PMID-16583246_T9", "type": "Protein", "text": [ "B4GALT7" ], "offsets": [ [ 928, 935 ] ], "normalized": [] }, { "id": "PMID-16583246_T10", "type": "Protein", "text": [ "beta4GalT-7" ], "offsets": [ [ 984, 995 ] ], "normalized": [] }, { "id": "PMID-16583246_T11", "type": "Protein", "text": [ "beta4GalT-7" ], "offsets": [ [ 1064, 1075 ] ], "normalized": [] }, { "id": "PMID-16583246_T12", "type": "Protein", "text": [ "decorin" ], "offsets": [ [ 1269, 1276 ] ], "normalized": [] }, { "id": "PMID-16583246_T13", "type": "Protein", "text": [ "beta4GalT-7" ], "offsets": [ [ 1292, 1303 ] ], "normalized": [] }, { "id": "PMID-16583246_T14", "type": "Protein", "text": [ "decorin" ], "offsets": [ [ 1344, 1351 ] ], "normalized": [] }, { "id": "PMID-16583246_T15", "type": "Protein", "text": [ "Biglycan" ], "offsets": [ [ 1425, 1433 ] ], "normalized": [] }, { "id": "PMID-16583246_T16", "type": "Protein", "text": [ "beta4GalT-7" ], "offsets": [ [ 1580, 1591 ] ], "normalized": [] }, { "id": "PMID-16583246_T17", "type": "Protein", "text": [ "decorin" ], "offsets": [ [ 1656, 1663 ] ], "normalized": [] }, { "id": "PMID-16583246_T18", "type": "Protein", "text": [ "biglycan" ], "offsets": [ [ 1668, 1676 ] ], "normalized": [] }, { "id": "PMID-16583246_T19", "type": "Protein", "text": [ "beta4GalT-7" ], "offsets": [ [ 1705, 1716 ] ], "normalized": [] }, { "id": "PMID-16583246_T20", "type": "Protein", "text": [ "beta4GalT-7" ], "offsets": [ [ 1953, 1964 ] ], "normalized": [] }, { "id": "PMID-16583246_T21", "type": "Protein", "text": [ "beta4GalT-7" ], "offsets": [ [ 2045, 2056 ] ], "normalized": [] }, { "id": "PMID-16583246_T22", "type": "Protein", "text": [ "beta4GalT-7" ], "offsets": [ [ 2087, 2098 ] ], "normalized": [] }, { "id": "PMID-16583246_T23", "type": "Protein", "text": [ "decorin" ], "offsets": [ [ 2148, 2155 ] ], "normalized": [] }, { "id": "PMID-16583246_T24", "type": "Protein", "text": [ "biglycan" ], "offsets": [ [ 2160, 2168 ] ], "normalized": [] }, { "id": "PMID-16583246_T25", "type": "Protein", "text": [ "beta4GalT-7" ], "offsets": [ [ 2227, 2238 ] ], "normalized": [] }, { "id": "PMID-16583246_T28", "type": "Entity", "text": [ "dermatan sulfate" ], "offsets": [ [ 617, 633 ] ], "normalized": [] } ]

[ { "id": "PMID-16583246_E1", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 10, 23 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16583246_T1" } ] }, { "id": "PMID-16583246_E2", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 10, 23 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16583246_T2" } ] }, { "id": "PMID-16583246_E3", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 596, 609 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16583246_T6" }, { "role": "Sidechain", "ref_id": "PMID-16583246_T28" } ] }, { "id": "PMID-16583246_E4", "type": "Glycosylation", "trigger": { "text": [ "monoglycanated" ], "offsets": [ [ 1449, 1463 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16583246_T15" } ] }, { "id": "PMID-16583246_E5", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 2131, 2144 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16583246_T23" } ] }, { "id": "PMID-16583246_E6", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 2131, 2144 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16583246_T24" } ] } ]

[]

[]

[ { "id": "PMID-16627342__text", "type": "abstract", "text": [ "Expression of aberrantly glycosylated tumor mucin-1 on human DC after transduction with a fiber-modified adenoviral vector. \nBACKGROUND: DC-presenting tumor Ag are currently being developed to be used as a vaccine in human cancer immunotherapy. To increase chances for successful therapy it is important to deliver full-length tumor Ag instead of loading single peptides. METHODS: In this study we used a fiber-modified adenoviral vector (rAd5F35) containing full-length tumor Ag cDNA to transduce human monocyte (Mo)-derived DC in vitro. Cells were efficiently transduced and survived for at least 3 days after adenoviral transduction. Phenotype and function after maturation of Mo-DC were not impaired by infection with adenovirus particles. Expression of the tumor-associated Ag mucin-1 (MUC1) was detected using MAb defining different MUC1 glycoforms. RESULTS: Non-transduced mature Mo-DC express endogenous MUC1 with normal glycosylation. After transduction with the rAd5F35-MUC1 adenoviral vector, Mo-DC also expressed MUC1 with tumor-associated glycosylation (Tn and T glycoforms), although no changes in mRNA levels of relevant glycosyltransferases could be demonstrated. DISCUSSION: The presence of aberrantly glycosylated MUC1 may influence Ag presentation of the tumor glycoforms of MUC1 to immune cells, affecting tumor cell killing. These findings could be highly relevant to developing strategies for cancer immunotherapy based on DC vaccines using MUC1 as tumor Ag.\n" ], "offsets": [ [ 0, 1481 ] ] } ]

[ { "id": "PMID-16627342_T1", "type": "Protein", "text": [ "mucin-1" ], "offsets": [ [ 44, 51 ] ], "normalized": [] }, { "id": "PMID-16627342_T2", "type": "Protein", "text": [ "mucin-1" ], "offsets": [ [ 782, 789 ] ], "normalized": [] }, { "id": "PMID-16627342_T3", "type": "Protein", "text": [ "MUC1" ], "offsets": [ [ 791, 795 ] ], "normalized": [] }, { "id": "PMID-16627342_T4", "type": "Protein", "text": [ "MUC1" ], "offsets": [ [ 839, 843 ] ], "normalized": [] }, { "id": "PMID-16627342_T5", "type": "Protein", "text": [ "MUC1" ], "offsets": [ [ 912, 916 ] ], "normalized": [] }, { "id": "PMID-16627342_T6", "type": "Protein", "text": [ "MUC1" ], "offsets": [ [ 980, 984 ] ], "normalized": [] }, { "id": "PMID-16627342_T7", "type": "Protein", "text": [ "MUC1" ], "offsets": [ [ 1025, 1029 ] ], "normalized": [] }, { "id": "PMID-16627342_T8", "type": "Protein", "text": [ "MUC1" ], "offsets": [ [ 1232, 1236 ] ], "normalized": [] }, { "id": "PMID-16627342_T9", "type": "Protein", "text": [ "MUC1" ], "offsets": [ [ 1294, 1298 ] ], "normalized": [] }, { "id": "PMID-16627342_T10", "type": "Protein", "text": [ "MUC1" ], "offsets": [ [ 1463, 1467 ] ], "normalized": [] } ]

[ { "id": "PMID-16627342_E1", "type": "Glycosylation", "trigger": { "text": [ "glycosylated" ], "offsets": [ [ 25, 37 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16627342_T1" } ] }, { "id": "PMID-16627342_E2", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 929, 942 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16627342_T5" } ] }, { "id": "PMID-16627342_E3", "type": "Glycosylation", "trigger": { "text": [ "glycosylation" ], "offsets": [ [ 1052, 1065 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16627342_T7" } ] }, { "id": "PMID-16627342_E4", "type": "Glycosylation", "trigger": { "text": [ "glycosylated" ], "offsets": [ [ 1219, 1231 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16627342_T8" } ] } ]

[ { "id": "PMID-16627342_1", "entity_ids": [ "PMID-16627342_T2", "PMID-16627342_T3" ] } ]

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[ { "id": "PMID-16632473__text", "type": "abstract", "text": [ "Dissecting the biological functions of Drosophila histone deacetylases by RNA interference and transcriptional profiling. \nZinc-dependent histone deacetylases (HDACs) are a family of hydrolases first identified as components of transcriptional repressor complexes, where they act by deacetylating lysine residues at the N-terminal extensions of core histones, thereby affecting transcription. To get more insight into the biological functions of the individual HDAC family members, we have used RNA interference in combination with microarray analysis in Drosophila S2 cells. Silencing of Drosophila HDAC1 (DHDAC1), but not of the other DHDAC family members, leads to increased histone acetylation. Silencing of either DHDAC1 or DHDAC3 leads to cell growth inhibition and deregulated transcription of both common and distinct groups of genes. Silencing DHDAC2 leads to increased tubulin acetylation levels but was not associated with a deregulation of gene expression. No growth of phenotype and no significant deregulation of gene expression was observed upon silencing of DHDAC4 and DHDACX. Loss of DHDAC1 or exposure of S2 cells to the small molecule HDAC inhibitor trichostatin both lead to a G(2) arrest and were associated with significantly overlapping gene expression signatures in which genes involved in nucleobase and lipid metabolism, DNA replication, cell cycle regulation, and signal transduction were over-represented. A large number of these genes were shown to also be deregulated upon loss of the co-repressor SIN3 (Pile, L. A., Spellman, P. T., Katzenberger, R. J., and Wassarman, D. A. (2003) J. Biol. Chem. 278, 37840-37848). We conclude the following. 1) DHDAC1 and -3 have distinct functions in the control of gene expression. 2) Under the tested conditions, DHDAC2, -4, and X have no detectable transcriptional functions in S2 cells. 3) The anti-proliferative and transcriptional effects of trichostatin are largely recapitulated by the loss of DHDAC1. 4) The deacetylase activity of DHDAC1 significantly contributes to the repressor function of SIN3.\n" ], "offsets": [ [ 0, 2076 ] ] } ]

[ { "id": "PMID-16632473_T1", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 50, 57 ] ], "normalized": [] }, { "id": "PMID-16632473_T2", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 138, 145 ] ], "normalized": [] }, { "id": "PMID-16632473_T3", "type": "Protein", "text": [ "histones" ], "offsets": [ [ 350, 358 ] ], "normalized": [] }, { "id": "PMID-16632473_T4", "type": "Protein", "text": [ "HDAC1" ], "offsets": [ [ 600, 605 ] ], "normalized": [] }, { "id": "PMID-16632473_T5", "type": "Protein", "text": [ "HDAC1" ], "offsets": [ [ 608, 613 ] ], "normalized": [] }, { "id": "PMID-16632473_T6", "type": "Protein", "text": [ "histone" ], "offsets": [ [ 678, 685 ] ], "normalized": [] }, { "id": "PMID-16632473_T7", "type": "Protein", "text": [ "HDAC1" ], "offsets": [ [ 720, 725 ] ], "normalized": [] }, { "id": "PMID-16632473_T8", "type": "Protein", "text": [ "HDAC3" ], "offsets": [ [ 730, 735 ] ], "normalized": [] }, { "id": "PMID-16632473_T9", "type": "Protein", "text": [ "HDAC2" ], "offsets": [ [ 854, 859 ] ], "normalized": [] }, { "id": "PMID-16632473_T10", "type": "Protein", "text": [ "HDAC4" ], "offsets": [ [ 1075, 1080 ] ], "normalized": [] }, { "id": "PMID-16632473_T11", "type": "Protein", "text": [ "HDACX" ], "offsets": [ [ 1086, 1091 ] ], "normalized": [] }, { "id": "PMID-16632473_T12", "type": "Protein", "text": [ "HDAC1" ], "offsets": [ [ 1102, 1107 ] ], "normalized": [] }, { "id": "PMID-16632473_T13", "type": "Protein", "text": [ "SIN3" ], "offsets": [ [ 1528, 1532 ] ], "normalized": [] }, { "id": "PMID-16632473_T14", "type": "Protein", "text": [ "HDAC1" ], "offsets": [ [ 1678, 1683 ] ], "normalized": [] }, { "id": "PMID-16632473_T15", "type": "Protein", "text": [ "-3" ], "offsets": [ [ 1688, 1690 ] ], "normalized": [] }, { "id": "PMID-16632473_T16", "type": "Protein", "text": [ "HDAC2" ], "offsets": [ [ 1783, 1788 ] ], "normalized": [] }, { "id": "PMID-16632473_T17", "type": "Protein", "text": [ "-4" ], "offsets": [ [ 1790, 1792 ] ], "normalized": [] }, { "id": "PMID-16632473_T18", "type": "Protein", "text": [ "X" ], "offsets": [ [ 1798, 1799 ] ], "normalized": [] }, { "id": "PMID-16632473_T19", "type": "Protein", "text": [ "HDAC1" ], "offsets": [ [ 1970, 1975 ] ], "normalized": [] }, { "id": "PMID-16632473_T20", "type": "Protein", "text": [ "HDAC1" ], "offsets": [ [ 2009, 2014 ] ], "normalized": [] }, { "id": "PMID-16632473_T21", "type": "Protein", "text": [ "SIN3" ], "offsets": [ [ 2070, 2074 ] ], "normalized": [] }, { "id": "PMID-16632473_T23", "type": "Entity", "text": [ "lysine residues" ], "offsets": [ [ 297, 312 ] ], "normalized": [] } ]

[ { "id": "PMID-16632473_E1", "type": "Deacetylation", "trigger": { "text": [ "deacetylating" ], "offsets": [ [ 283, 296 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16632473_T3" }, { "role": "Site", "ref_id": "PMID-16632473_T23" } ] }, { "id": "PMID-16632473_E2", "type": "Acetylation", "trigger": { "text": [ "acetylation" ], "offsets": [ [ 686, 697 ] ] }, "arguments": [ { "role": "Theme", "ref_id": "PMID-16632473_T6" } ] } ]

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[ { "id": "PMID-16686428__text", "type": "abstract", "text": [ "Regulation of HIF: asparaginyl hydroxylation. \nThe hypoxia inducible transcription factors (HIFs) are regulated at the level of protein stability and transcriptional activity in an oxygen-dependent manner by prolyl and asparaginyl hydroxylation, respectively. Factor inhibiting HIF (FIH-1) is the only known HIF asparaginyl hydroxylase, and targets a conserved asparaginyl residue within the C-terminal activation domain (CAD) of HIF-alpha. This represses HIF-mediated transcription by inhibiting the recruitment of p300/CBP coactivators. Recent studies have demonstrated that the function of FIH-1 relative to the HIF prolyl hydroxylases (PHDs) is not redundant, and indicate that FIH-1 is a direct oxygen sensor. This paper will address recent published and unpublished work characterising the role of asparaginyl hydroxylation in the cellular response to hypoxia. The relative oxygen affinities and hypoxic activities of FIH-1 and the PHDs will be discussed. Furthermore, in vitro and cell-based assays demonstrating some novel characteristics regarding the substrate specificity of FIH-1, and their potential biological and therapeutic relevance will be presented.\n" ], "offsets": [ [ 0, 1169 ] ] } ]

[ { "id": "PMID-16686428_T1", "type": "Protein", "text": [ "Factor inhibiting HIF" ], "offsets": [ [ 260, 281 ] ], "normalized": [] }, { "id": "PMID-16686428_T2", "type": "Protein", "text": [ "FIH-1" ], "offsets": [ [ 283, 288 ] ], "normalized": [] }, { "id": "PMID-16686428_T3", "type": "Protein", "text": [ "HIF asparaginyl hydroxylase" ], "offsets": [ [ 308, 335 ] ], "normalized": [] }, { "id": "PMID-16686428_T4", "type": "Protein", "text": [ "p300" ], "offsets": [ [ 516, 520 ] ], "normalized": [] }, { "id": "PMID-16686428_T5", "type": "Protein", "text": [ "CBP" ], "offsets": [ [ 521, 524 ] ], "normalized": [] }, { "id": "PMID-16686428_T6", "type": "Protein", "text": [ "FIH-1" ], "offsets": [ [ 593, 598 ] ], "normalized": [] }, { "id": "PMID-16686428_T7", "type": "Protein", "text": [ "FIH-1" ], "offsets": [ [ 682, 687 ] ], "normalized": [] }, { "id": "PMID-16686428_T8", "type": "Protein", "text": [ "FIH-1" ], "offsets": [ [ 924, 929 ] ], "normalized": [] }, { "id": "PMID-16686428_T9", "type": "Protein", "text": [ "FIH-1" ], "offsets": [ [ 1086, 1091 ] ], "normalized": [] } ]

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[ { "id": "PMID-16686428_1", "entity_ids": [ "PMID-16686428_T1", "PMID-16686428_T2", "PMID-16686428_T3" ] } ]

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[ { "id": "PMID-16717435__text", "type": "abstract", "text": [ "Production of three O-methhylated esculetins with Escherichia coli expressing O-methyltransferase from poplar. \nO-Methyltransferase, POMT-9 was expressed in Escherichia coli. HPLC analysis of reaction products revealed three peaks corresponding to isoscopoletin, scopoletin, and scoparone, and their structures were determined using NMR. Biotransformation of esculetin with E. coli expressing POMT-9 generated scopoletin, isoscopoletin, and scoparone at 30.3, 21, and 31 microM respectively. POMT-9 is the first O-methyltransferase that produces three different O-methylated products.\n" ], "offsets": [ [ 0, 585 ] ] } ]

[ { "id": "PMID-16717435_T1", "type": "Protein", "text": [ "POMT-9" ], "offsets": [ [ 133, 139 ] ], "normalized": [] }, { "id": "PMID-16717435_T2", "type": "Protein", "text": [ "POMT-9" ], "offsets": [ [ 393, 399 ] ], "normalized": [] }, { "id": "PMID-16717435_T3", "type": "Protein", "text": [ "POMT-9" ], "offsets": [ [ 492, 498 ] ], "normalized": [] } ]

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