TASK DEFINITION: Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: Context: DNA methylation at CpG dinucleotides is modified in tumorigenesis with potential impact on transcriptional activity.', 'We used the Illumina 450 K platform to evaluate DNA methylation patterns of 50 metastatic melanoma tumors, with matched gene expression data.', 'We identified three different methylation groups and validated the groups in independent data from The Cancer Genome Atlas. One group displayed hypermethylation of a developmental promoter set, genome-wide demethylation, increased proliferation and activity of the SWI/SNF complex. A second group had a methylation pattern resembling stromal and leukocyte cells, over-expressed an immune signature and had improved survival rates in metastatic tumors (p < 0.05). A third group had intermediate methylation levels and expressed both proliferative and immune signatures. The methylation groups corresponded to some degree with previously identified gene expression phenotypes.
Answer: Melanoma consists of divergent methylation groups that are distinguished by promoter methylation, proliferation and content of immunological cells.

SOLUTION: Are dNA methylation subgroups in melanoma associated with proliferative and immunological processes?

PROBLEM: Context: Alterations in epigenetic processes are frequently noted in human disease. These epigenetic processes involve methylation of DNA and post-translational modifications of histones. It is well established that in particular histone methylation plays a key role in gene transcription. In this study, we have investigated the relationship between triple methylation of lysine 27 in histone H3 (H3K27Me3) modifications and atherosclerotic plaque stage.', '28 peri-renal aortic tissue patches covering the entire spectrum of atherosclerotic plaque development were evaluated by immunohistochemistry for the levels of H3K27Me3, EZH2, JMJD3 and BMI1.', 'The results of our studies are in support of a reduction in global levels of the H3K27Me3 modification in vessels with advanced atherosclerotic plaques. This reduction in H3K27Me3 levels is not accompanied by alterations in global levels of the corresponding histone methyltransferase EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2). Likewise no alterations in global levels of BMI1, a component of the PRC1 complex, which binds to H3K27Me3-modified histones or the global expression levels of the histone demethylase JMJD3, which removes the methyl marks on H3K27, were observed.
Answer: Together, our data show that in atherosclerosis development alterations in global levels of H3K27Me3 occur. The reduction in the number of nuclei in the tunica media that display the repressive H3K27Me3 mark in vessels with advanced atherosclerosis plaques therefore could be a reflection of the dynamic pattern of smooth muscle cell differentiation and proliferation associated with atherosclerotic disease.

SOLUTION: Are global histone H3 lysine 27 triple methylation levels reduced in vessels with advanced atherosclerotic plaques?

PROBLEM: Context: Because accumulation of extracellular matrix is a prominent characteristic of the microangiopathy that complicates long-term diabetes, a pathogenetic role for transforming growth factor beta (TGF-beta) is being considered. Having observed that glucose levels mimicking diabetic hyperglycemia induce in vitro endothelial cell overexpression of extracellular matrix molecules, decreased replication, and increased levels of TGF-beta mRNA, we have examined whether the effects of high glucose are mediated by autocrine TGF-beta.', 'TGF-beta levels were measured by bioassay in the media conditioned by human umbilical vein endothelial cells cultured in the presence of high (30 mM) or normal (5 mM) glucose concentrations. The effect of high glucose was tested on the proliferation of two epithelial cell lines, one (Mv1Lu) exquisitely sensitive to TGF-beta and the other (DR mutants) insensitive to the cytokine. To examine whether high glucose and TGF-beta affect cellular programs in a similar manner, the effects of high glucose and exogenous TGF-beta were compared on proliferation and gene expression of endothelial cells.', 'Media conditioned by endothelial cells cultured in high or normal glucose contained similar amounts of TGF-beta (4.9 +/- 3.5 and 3.7 +/- 2.5 ng/10(6) cells, respectively (mean +/- SD)), all in the latent form. The replication of parental Mv1Lu cells and their DR mutants was decreased by high glucose to the same extent. Whereas the inhibitory effect of high glucose on endothelial cell replication was reversible, that of TGF-beta was not. Both perturbations induced up-regulation of fibronectin expression, but the effects were additive. Only TGF-beta induced overexpression of Type IV collagenase.
Answer: These combined observations indicate that (a) endothelial cells exposed to high glucose do not secrete TGF-beta in excess of control cells, (b) there are growth-inhibitory effects of high glucose that are independent of TGF-beta, and (c) high glucose and TGF-beta exert their effects through distinct pathways and at different loci.

SOLUTION:
Are the effects of high glucose on human endothelial cell growth and gene expression mediated by transforming growth factor-beta?