tbuckley/cabot-search huggingface dataset:
Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer GroupAnn Oncol 2003; 14: 441–448
Authors: M.S. Aapro, F.H. van Wijk, G. Bolis, B. Chevallier, M.E.L. van der Burg, A. Poveda, C.F. de Oliveira, S. Tumolo, V. Scotto di Palumbo, M. Piccart, M. Franchi, F. Zanaboni, A.J. Lacave, R. Fontanelli, G. Favalli, P. Zola, J.P. Guastalla, R. Rosso, C. Marth, M. Nooij, M. Presti, C. Scarabelli, T.A.W. Splinter, E. Ploch, L.V.A. Beex, W. ten Bokkel Huinink, M. Forni, M. Melpignano, P. Blake, P. Kerbrat, C. Mendiola, A. Cervantes, A. Goupil, P.G. Harper, C. Madronal, M. Namer, G. Scarfone, J.E.G.M. Stoot, I. Teodorovic, C. Coens, I. Vergote, J.B. Vermorken
Journal: Annals of Oncology (2003)

The authors wish to correct the authorship of the above paper. The first and second authors should be transposed so that the correct order is as follows: F. H. van Wijk, M. S. Aapro, G. Bolis, B. Chevallier, M. E. L. van der Burg, A. Poveda, C. F. de Oliveira, S. Tumolo, V. Scotto di Palumbo, M. Piccart, M. Franchi, F. Zanaboni, A. J. Lacave,R. Fontanelli, G. Favalli, P. Zola, J. P. Guastalla, R. Rosso,C. Marth, M. Nooij, M. Presti, C. Scarabelli, T. A. W. Splinter,E. Ploch, L. V. A. Beex, W. ten Bokkel Huinink, M. Forni, M. Melpignano, P. Blake, P. Kerbrat, C. Mendiola, A. Cervantes, A. Goupil, P. G. Harper, C. Madronal, M. Namer, G. Scarfone, J. E. G. M. Stoot, I. Teodorovic, C. Coens, I. Vergote &J. B. Vermorken On behalf of the European Organisation for Research and Treatment of Cancer (EORTC) Gynaecological Cancer Group
Cyclooxygenase Inhibition Increases Interleukin 5 and Interleukin 13 Production and Airway Hyperresponsiveness in Allergic Mice
Authors: R. STOKES PEEBLES, RYSZARD DWORSKI, ROBERT D. COLLINS, KASIA JARZECKA, DAPHNE B. MITCHELL, BARNEY S. GRAHAM, JAMES R. SHELLER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The immunomodulatory role of arachidonic acid metabolites in allergic sensitization is undefined. Prostaglandin E2 (PGE2), a product of arachidonic acid metabolism through the cyclooxygenase pathway, has been reported to favor Type 2-like cytokine secretion profiles in murine and human CD4+ T cells by inhibiting the production of Type 1-associated cytokines. On the basis of these in vitro data, we hypothesized that indomethacin, a nonselective cyclooxygenase inhibitor, would diminish allergen-induced production of Type 2 cytokines in mice, and protect against airway hyperresponsiveness (AHR) to methacholine. We found that ovalbumin-sensitized mice that were treated with indomethacin (OVA–indomethacin mice) had significantly greater AHR (p < 0.05) and higher levels of IL-5 (176 ± 52 versus 66 ± 4 pg/ml) and IL-13 (1,226 ± 279 versus 475 ± 65 pg/ml) in lung supernatants than mice sensitized with ovalbumin alone (OVA mice), while levels of IL-4 and serum IgE were not different. Lung mRNA expression of the C-C chemokine MCP-1 was increased in OVA–indomethacin mice, while there was no difference between the two groups in lung mRNA expression of eotaxin, MIP-1 α , MIP-1 β , or MIP-2. Histologic examination revealed greater pulmonary interstitial eosinophilia in OVA–indomethacin mice as well. Contrary to our expectations, we conclude that in the BALB/c mouse, cyclooxygenase inhibition during allergen sensitization increases AHR, production of IL-5 and IL-13, and interstitial eosinophilia.
Benefits from Adding the 5-Lipoxygenase Inhibitor Zileuton to Conventional Therapy in Aspirin-intolerant Asthmatics
Authors: BARBRO DAHLÉN, EWA NIZANKOWSKA, ANDREW SZCZEKLIK, OLLE ZETTERSTRÖM, GRAZYNA BOCHENEK, MARIA KUMLIN, LUCYNA MASTALERZ, GRAZYNA PINIS, LINDA J. SWANSON, TERRY I. BOODHOO, STEPHEN WRIGHT, LOUISE M. DUBÉ, SVEN-ERIK DAHLÉN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

From bronchoprovocation studies and investigations of the acute effects of drugs that inhibit leukotrienes (LT), the hypothesis has emerged that leukotrienes are important mediators of airway obstruction and other symptoms in aspirin-intolerant asthma (AIA). However, it has yet not been shown if subjects with AIA respond favorably to clinical treatment with leukotriene inhibitors. Therefore, in a double-blind placebo-controlled crossover study, we examined the effects of 6 wk of treatment with the leukotriene-pathway inhibitor zileuton (600 mg, four times daily) in 40 patients with well-characterized AIA. The treatment was added to existing therapy, which included medium to high doses of inhaled (average daily dose 1,030 μ g of beclomethasone or budesonide) or oral glucocorticosteroids (4 to 25 mg/d) for all but one of the patients. On top of this treated baseline, there were no significant effects of adding placebo, indicating that their asthma was kept relatively stable. However, there was an acute and chronic improvement in pulmonary function after treatment with zileuton, expressed both as increased FEV1 from baseline compared with placebo, and higher morning and evening peak expiratory flow rate (PEFR) values on zileuton treatment compared with placebo. The improvements occurred despite lower use of rescue bronchodilator with zileuton. Zileuton also diminished nasal dysfunction, which is one of the cardinal signs of AIA. There was a remarkable return of smell, less rhinorrhea, and a trend for less stuffiness and higher nasal inspiratory flow during treatment with zileuton. Zileuton caused a small but distinct reduction of bronchial hyperresponsiveness to histamine and inhibited aspirin-induced bronchoconstriction. Zileuton inhibited urinary excretion of LTE4 but did not change airway reactivity to inhaled LTD4 , supporting that zileuton specifically inhibited leukotriene biosynthesis. The findings indicate that leukotrienes are important mediators of persistent airway obstruction and chronic nasal dysfunction in AIA. The study also suggests that addition of a leukotriene pathway inhibitor such as zileuton may bring about greater control of asthma than what is achieved by treatment with medium to high doses of glucocorticosteroids alone.
Lessons Learned From a Clinical Trial
Authors: Paul W. Armstrong, L. Kristin Newby, Christopher B. Granger, Kerry L. Lee, R. John Simes, Frans Van de Werf, Harvey D. White, Robert M. Califf
Journal: Circulation (2004)

R emarkable advances in cardiovascular care have been substantially mediated by large-scale, randomized clinical trials.These trials not only have identified treatments resulting in major improvements in patient outcomes but also have enhanced our understanding of the natural history of contemporary disease and the impact of risk factors and complications.The process by which phase III clinical trials in cardiovascular medicine are created, implemented, completed, analyzed, presented, and published has evolved dramatically over the past decade.Historically, government and academic alliances took center stage in this process because of their intellectual equity, opinion leadership, access to patients, and allocation of public interest-related research tax dollars.This axis has now shifted.Community practitioners and groups of physicians, often organized regionally, now provide the majority of subjects for clinical trials.Furthermore, substantial scientific expertise, at both the basic and clinical levels, resides within multinational pharmaceutical firms.Additionally, contract research organizations have seized the business opportunity afforded by the need for timely and efficient operational aspects of clinical trials.Although communitybased trials, efficiency, and expertise are prerequisites for a major clinical trial, the extraordinary costs of completing them squarely places the sponsor in a dominant position. 1ur participation in the failed large-scale attempt to develop a novel oral glycoprotein IIb/IIIa inhibitor, sibrafiban, for secondary prevention of coronary heart disease has stimulated us to reflect on issues that arose in the design and conduct of this trial. 2,3Using the Sibrafiban Versus Aspirin to Yield Maximum Protection From ischemic Heart Events Post-Acute Coronary Syndromes (SYMPHONY) and 2nd SYMPHONY trials as examples, we review issues here that should be of interest to investigators, clinical practitioners, participating institutions, sponsors, data and safety monitoring boards (DSMBs), and the patients whom we serve. 4Our purpose is to encourage discussion so that standards can be enhanced for this form of collaborative science.
75 CROSS SECTIONAL ANALYSIS OF THE PREVALENCE AND CHARACTER OF HEPATITIS B VIRUS INFECTION IN HIV-INFECTED AND HIV-UNINFECTED PREGNANT WOMEN IN THE WESTERN CAPE, SOUTH AFRICA
Authors: M.I. Andersson, T.G. Maponga, S. Ijaz, G. Theron, W. Preiser, R.S. Tedder
Journal: Journal of Hepatology (2012)
Chronic IFN-γ production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1/PU.1 axis
Authors: Sten F. Libregts, Laura Gutiérrez, Alexander M. de Bruin, Felix M. Wensveen, Petros Papadopoulos, Wilfred van Ijcken, Zeliha Özgür, Sjaak Philipsen, Martijn A. Nolte
Journal: Blood (2011)
Effect of CPAP on pericardial pressure and respiratory system mechanics in pigs.
Authors: S I Huberfeld, J Genovese, A Tarasiuk, S M Scharf
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

It has been postulated that increased cardiac surface pressure with continuous positive airway pressure (CPAP) results in decreased left-ventricular (LV) transmural pressure. We tested this hypothesis in seven sedated, unanesthetized, and previously instrumented pigs. We measured pericardial (Pperi), LV, airway (P(aw)), and esophageal (Pes) pressures at CPAP values of 0, 4, 8, and 12 cm H2O before and after blood-volume expansion. With normovolemia, CPAP resulted in an increase in Pperi (from -2.0 +/- 7.6 mm Hg at CPAP 0 to 2.3 +/- 5.6 mmHg at CPAP 12, p < 0.05). Baseline end-diastolic Pperi rose with volume expansion from -2.0 +/- 7.6 mm Hg to 5.4 +/- 5.4 mm Hg, p < 0.05. With hypervolemia, CPAP was associated with a decrease in Pperi (from 5.42 +/- 5.4 mm Hg to 2.3 +/- 5.6 mm Hg, p < 0.05). By contrast, Pes rose equally under both conditions with CPAP. LV transmural end-diastolic pressure (TMEDP) fell significantly under normovolemic conditions (from 16.5 +/- 7.4 mm Hg at CPAP 0 to 13.6 +/- 9.0 mm Hg at CPAP 12). The changes in FRC (pneumotachometry) with CPAP were similar under both conditions. We conclude that the CPAP-induced decrease in LV volume under hypervolemic conditions cannot be explained by an increase in cardiac surface pressure. We present a model to explain the decrease in cardiac surface pressure with CPAP.
Enhanced ERK-1/2 activation in mice susceptible to coxsackievirus-induced myocarditis
Authors: Mary Anne Opavsky, Tami Martino, Marlene Rabinovitch, Josef Penninger, Chris Richardson, Martin Petric, Cathy Trinidad, Lisa Butcher, Janice Chan, Peter P. Liu
Journal: Journal of Clinical Investigation (2002)

Group B coxsackieviral (CVB) infection commonly causes viral myocarditis. Mice are protected from CVB3 myocarditis by gene-targeted knockout of p56Lck(Lck), the Src family kinase (Src) essential for T cell activation. Extracellular signal-regulated kinase 1 and 2 (ERK-1/2) can influence cell function downstream of Lck. Using T cell lines and neonatal cardiac myocytes we investigated the role of ERK-1/2 in CVB3 infection. In Jurkat T cells ERK-1/2 is rapidly activated by CVB3; but, this response is absent in Lck-negative JCaM T cells. Inhibition of ERK-1/2 with UO126 reduced CVB3 titers in Jurkat cells, but not in JCaM cells. In cardiac myocytes CVB3 activation of ERK-1/2 is blocked by the Src inhibitor PP2. In addition, viral production in myocytes is decreased by Src or ERK-1/2 inhibition. In vitro, in both immune and myocardial cells, ERK-1/2 is activated by CVB3 downstream of Lck and other Src’s and is necessary for efficient CVB3 replication. In vivo, following CVB3 infection, ERK-1/2 activation is evident in the myocardium. ERK-1/2 activation is intense in the hearts of myocarditis-susceptible A/J mice. In contrast, significantly less ERK-1/2 activation is found in the hearts of myocarditis-resistant C57BL/6 mice. Therefore, the ERK-1/2 response to CVB3 infection may contribute to differential host susceptibility to viral myocarditis.
Association Between Family Structure, Parental Smoking, Friends Smoking and Smoking Habits in Asthmatic Adolescents
Authors: F VAZQUEZNAVA, F BELTRANGUZMAN, A SALDIVARGONZALEZ, C VAZQUEZRODRIGUEZ, E VAZQUEZRODRIGUEZ, V ALMEIDAARVIZU, M BARRIENTOSGOMEZ, D LINOCHOA
Journal: Journal of Allergy and Clinical Immunology (2008)
Part 4: Conflict of Interest Management Before, During, and After the 2010 International Consensus Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations
Authors: John E. Billi, Michael Shuster, Leo Bossaert, Allan R. de Caen, Charles D. Deakin, Brian Eigel, Mary Fran Hazinski, Robert W. Hickey, Ian Jacobs, Monica E. Kleinman, Rudolph W. Koster, Mary E. Mancini, William H. Montgomery, Peter T. Morley, Laurie J. Morrison, Henrietta Munoz, Vinay M. Nadkarni, Jerry P. Nolan, Robert E. O'Connor, Jeffrey M. Perlman, Sam Richmond, Michael R. Sayre, Jasmeet Soar, Jonathan Wyllie, David Zideman
Journal: Circulation (2010)
FoxM1 and Wnt/β-Catenin Signaling in Glioma Stem Cells
Authors: Aihua Gong, Suyun Huang
Journal: Cancer Research (2012)

Abstract Cancer stem cells may be responsible for tumor initiation and maintenance. The molecular mechanisms that control cancer stem cells are related to alterations in various signaling pathways, including the Wnt/β-catenin signaling pathway. The canonical Wnt/β-catenin signaling pathway is one of the major signaling systems in stem and progenitor cells, and aberrant activation of the Wnt/β-catenin signaling pathway is common in human cancers. As with β-catenin, FoxM1 has been found to play important roles in a number of cancers. In this review, we discuss the evidence that FoxM1 affects the expression and function of a variety of genes that are critical to the survival, proliferation, invasion, angiogenesis, and self-renewal of cancer stem cells. We highlight the pivotal roles of the Wnt/β-catenin and FoxM1 signaling pathways in neural stem and progenitor cells and glioma stem cells. We also discuss the evidence for cross-talk between the β-catenin and FoxM1 signaling pathways in the regulation of the stemness and tumorigenicity of glioma stem cells. Cancer Res; 72(22); 5658–62. ©2012 AACR.
Anthropometric characteristics of elite male junior rowers
Authors: Jan Bourgois, Albrecht L Claessens, Jacques Vrijens, Renaat Philippaerts, Bart Van Renterghem, Martine Thomis, Melissa Janssens, Ruth Loos, Johan Lefevre
Journal: British Journal of Sports Medicine (2000)

During the 1997 Fédération Internationale des Sociétés d'Aviron World Junior Rowing Championships, anthropometric data on 383 male junior rowers were assessed. With 430 participating athletes, the sample represented 89% of the population. In addition to age, 27 dimensions were measured: body mass, six heights or lengths, four breadths, 10 girths, and six skinfolds. The elite male junior rowers were tall (187.4 (5.8) cm; mean (SD)) and heavy (82.2 (7.4) kg), with larger length, breadth, and girth dimensions than a nationally representative sample of Belgian boys of the same chronological age. A rowing specific anthropometric profile chart with norms was constructed. The stature of the junior rowers is similar to that of adult heavyweight elite rowers, except that the junior rowers are lighter. Compared with non-finalists, finalists are heavier (but still lighter than the adult heavyweight elite rower) and taller, with greater length, breadth (except for the bicristal diameter), and girth dimensions.
Pathogenesis of an Infectious Mononucleosis-like Disease Induced by a Murine γ-Herpesvirus: Role for a Viral Superantigen?
Authors: Ralph A. Tripp, Ann Marie Hamilton-Easton, Rhonda D. Cardin, Phuong Nguyen, Frederick G. Behm, David L. Woodland, Peter C. Doherty, Marcia A. Blackman
Journal: The Journal of Experimental Medicine (1997)

The murine γ-herpesvirus 68 has many similarities to EBV, and induces a syndrome comparable to infectious mononucleosis (IM). The frequency of activated CD8+ T cells (CD62Llo) in the peripheral blood increased greater than fourfold by 21 d after infection of C57BL/6J (H-2b) mice, and remained high for at least a further month. The spectrum of T cell receptor usage was greatly skewed, with as many as 75% of the CD8+ T cells in the blood expressing a Vβ4+ phenotype. Interestingly, the Vβ4 dominance was also seen, to varying extents, in H-2k, H-2d, H-2u, and H-2q strains of mice. In addition, although CD4 depletion from day 11 had no effect on the Vβ4 bias of the T cells, the Vβ4+CD8+ expansion was absent in H-2IAb–deficient congenic mice. However, the numbers of cycling cells in the CD4 antibody–depleted mice and mice that are CD4 deficient as a consequence of the deletion of MHC class II, were generally lower. The findings suggest that the IM-like disease is driven both by cytokines provided by CD4+ T cells and by a viral superantigen presented by MHC class II glycoproteins to Vβ4+CD8+ T cells.
Fcα/μ receptor mediates endocytosis of IgM-coated microbes
Authors: Akira Shibuya, Norihisa Sakamoto, Yoshio Shimizu, Kazuko Shibuya, Mitsujiro Osawa, Takashi Hiroyama, Helen J. Eyre, Grant R. Sutherland, Yuichi Endo, Teizo Fujita, Tomoyuki Miyabayashi, Seiji Sakano, Takao Tsuji, Eiichi Nakayama, Joseph H. Phillips, Lewis L. Lanier, Hiromitsu Nakauchi
Journal: Nature Immunology (2000)
<i>GRHL1</i>Acts as Tumor Suppressor in Neuroblastoma and Is Negatively Regulated by MYCN and HDAC3
Authors: Johannes Fabian, Marco Lodrini, Ina Oehme, Marie C. Schier, Theresa M. Thole, Thomas Hielscher, Annette Kopp-Schneider, Lennart Opitz, David Capper, Andreas von Deimling, Inga Wiegand, Till Milde, Ulrich Mahlknecht, Frank Westermann, Odilia Popanda, Frederik Roels, Barbara Hero, Frank Berthold, Matthias Fischer, Andreas E. Kulozik, Olaf Witt, Hedwig E. Deubzer
Journal: Cancer Research (2014)

Neuroblastoma is an embryonic solid tumor of neural crest origin and accounts for 11% of all cancer-related deaths in children. Novel therapeutic strategies are therefore urgently required. MYCN oncogene amplification, which occurs in 20% of neuroblastomas, is a hallmark of high risk. Here, we aimed to exploit molecular mechanisms that can be pharmacologically addressed with epigenetically modifying drugs, such as histone deacetylase (HDAC) inhibitors. Grainyhead-like 1 (GRHL1), a gene critical for Drosophila neural development, belonged to the genes most strongly responding to HDAC inhibitor treatment of neuroblastoma cells in a genome-wide screen. An increase in the histone H4 pan-acetylation associated with its promoter preceded transcriptional activation. Physically adjacent, HDAC3 and MYCN colocalized to the GRHL1 promoter and repressed its transcription. High-level GRHL1 expression in primary neuroblastomas correlated on transcriptional and translational levels with favorable patient survival and established clinical and molecular markers for favorable tumor biology, including lack of MYCN amplification. Enforced GRHL1 expression in MYCN-amplified neuroblastoma cells with low endogenous GRHL1 levels abrogated anchorage-independent colony formation, inhibited proliferation, and retarded xenograft growth in mice. GRHL1 knockdown in MYCN single-copy cells with high endogenous GRHL1 levels promoted colony formation. GRHL1 regulated 170 genes genome-wide, and most were involved in pathways regulated during neuroblastomagenesis, including nervous system development, proliferation, cell-cell adhesion, cell spreading, and cellular differentiation. In summary, the data presented here indicate a significant role of HDAC3 in the MYCN-mediated repression of GRHL1 and suggest drugs that block HDAC3 activity and suppress MYCN expression as promising candidates for novel treatment strategies of high-risk neuroblastoma.
Self-assembled magnetic fluorescent polymeric micelles for magnetic resonance and optical imaging
Authors: Kai Yan, Huan Li, Penghui Li, Haie Zhu, Jie Shen, Changfeng Yi, Shuilin Wu, Kelvin W.K. Yeung, Zushun Xu, Haibo Xu, Paul K. Chu
Journal: Biomaterials (2013)
Influence of Lipid-Lowering Therapy on the Progression of Coronary Artery Calcification
Authors: Stephan Achenbach, Dieter Ropers, Karsten Pohle, Alexander Leber, Christian Thilo, Andreas Knez, Theresa Menendez, Ralph Maeffert, Magda Kusus, Matthias Regenfus, Andrea Bickel, Ralph Haberl, Gerhard Steinbeck, Werner Moshage, Werner G. Daniel
Journal: Circulation (2002)

Background— Coronary calcification measured by fast computed tomography techniques is a surrogate marker of coronary atherosclerotic plaque burden. In a cohort study, we prospectively investigated whether lipid-lowering therapy with a cholesterol synthesis enzyme inhibitor reduces the progression of coronary calcification. Methods and Results— In 66 patients with coronary calcifications in electron beam tomography (EBT), LDL cholesterol &gt;130 mg/dL, and no lipid-lowering treatment, the EBT scan was repeated after a mean interval of 14 months and treatment with cerivastatin was initiated (0.3 mg/d). After 12 months of treatment, a third EBT scan was performed. Coronary calcifications were quantified using a volumetric score. Cerivastatin therapy lowered the mean LDL cholesterol level from 164±30 to 107±21 mg/dL. The median calcified volume was 155 mm 3 (range, 15 to 1849) at baseline, 201 mm 3 (19 to 2486) after 14 months without treatment, and 203 mm 3 (15 to 2569) after 12 months of cerivastatin treatment. The median annualized absolute increase in coronary calcium was 25 mm 3 during the untreated versus 11 mm 3 during the treatment period ( P =0.01). The median annual relative increase in coronary calcium was 25% during the untreated versus 8.8% during the treatment period ( P &lt;0.0001). In 32 patients with an LDL cholesterol level &lt;100 mg/dL under treatment, the median relative change was 27% during the untreated versus −3.4% during the treatment period ( P =0.0001). Conclusions— Treatment with the cholesterol synthesis enzyme inhibitor cerivastatin significantly reduces coronary calcium progression in patients with LDL cholesterol &gt;130 mg/dL.
Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes
Authors: James P Reddington, Sara M Perricone, Colm E Nestor, Judith Reichmann, Neil A Youngson, Masako Suzuki, Diana Reinhardt, Donncha S Dunican, James G Prendergast, Heidi Mjoseng, Bernard H Ramsahoye, Emma Whitelaw, John M Greally, Ian R Adams, Wendy A Bickmore, Richard R Meehan
Journal: Genome biology (2013)

DNA methylation and the Polycomb repression system are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. By genome-wide mapping of the Polycomb Repressive Complex 2-signature histone mark, H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that hypomethylation leads to widespread H3K27me3 redistribution, in a manner that reflects the local DNA methylation status in wild-type cells. Unexpectedly, we observe striking loss of H3K27me3 and Polycomb Repressive Complex 2 from Polycomb target gene promoters in DNA hypomethylated cells, including Hox gene clusters. Importantly, we show that many of these genes become ectopically expressed in DNA hypomethylated cells, consistent with loss of Polycomb-mediated repression. An intact DNA methylome is required for appropriate Polycomb-mediated gene repression by constraining Polycomb Repressive Complex 2 targeting. These observations identify a previously unappreciated role for DNA methylation in gene regulation and therefore influence our understanding of how this epigenetic mechanism contributes to normal development and disease.