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A bivalent chromatin structure marks key developmental genes in embryonic stem cells, Cell 125
, 2006
"... The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by ex ..."
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The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. We identified a specific modification pattern, termed ‘‘bivalent domains,’ ’ consisting of large regions of H3 lysine 27 methylation harboring smaller regions of H3 lysine 4 methylation. Bivalent domains tend to coincide with TF genes expressed at low levels. We propose that bivalent domains silence developmental genes in ES cells while keeping them poised for activation. We also found striking correspondences between genome sequence and histone methylation in ES cells, which become notably weaker in differentiated cells. These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency.
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, 2009
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unknown title
, 2005
"... Transcriptional profiling of reporter genes used for molecular imaging of embryonic stem cell transplantation ..."
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Transcriptional profiling of reporter genes used for molecular imaging of embryonic stem cell transplantation
Pou5f1 Post-translational Modifications Modulate Gene Expression and Cell Fate
"... e533. All works published in PloSOne are open access, licensed under the Creative Commons Attribution License. Everything is immediately available without cost to anyone, anywhere-to read, download, redistribute, include in databases, and otherwise use-provided that the original author and source ar ..."
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e533. All works published in PloSOne are open access, licensed under the Creative Commons Attribution License. Everything is immediately available without cost to anyone, anywhere-to read, download, redistribute, include in databases, and otherwise use-provided that the original author and source are credited. Copyright is retained by the author. iii Embryonic stem cells (ESCs) are characterized by their unlimited capacity for self-renewal and the ability to contribute to every lineage of the developing embryo. The promoters of developmentally regulated loci within these cells are marked by coincident epigenetic modifications of gene activation and repression, termed bivalent domains. Trithorax group (TrxG) and Polycomb Group (PcG) proteins respectively place these epigenetic marks on chromatin and extensively colocalize with Oct4 in ESCs. Although it appears that these cells are poised and ready for differentiation, the switch that permits this transition is critically held in check. The derepression of bivalent domains upon knockdown
Review and report series of t4- the
"... transatlantic think tank for toxicology Kick-off paper: ..."
Phosphoproteome of Embryonic Stem Cells
"... ison yielded almost no consensus, suggesting that the stem cell phenotype cannot be explained by transcriptional profile alone (14, 15). Clearly mechanisms operating at the posttranscriptional level may also be relevant. To date, proteomic analysis of embryonic stem cells has been limited. Guo et al ..."
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ison yielded almost no consensus, suggesting that the stem cell phenotype cannot be explained by transcriptional profile alone (14, 15). Clearly mechanisms operating at the posttranscriptional level may also be relevant. To date, proteomic analysis of embryonic stem cells has been limited. Guo et al. (16) used comparative two-dimensional gel electrophoresis (2DGE) to examine the differentiation of ESCs into neural cells under retinoic acid treatment and found 24 differentially expressed spots of which 12 were identified. Elliott et al. (17) produced a two-dimension gel electrophoresis map of proteins in the mouse ESC line R1 and identified 218 proteins. Recently Nagano et al. (18) used 2D LC-MS/MS to identify �1800 proteins from the ESC line E14-1. 35 of these proteins yielded mass spectra that were consistent with phosphorylation, and one phosphorylation
JCB: ARTICLE
, 2005
"... MyoD induces myogenic differentiation through cooperation of its NH2- and COOH-terminal regions ..."
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MyoD induces myogenic differentiation through cooperation of its NH2- and COOH-terminal regions
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"... Abstract Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array ), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, OR G-allele = 1.13, P meta = 1.60 × 10 −8 ..."
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Abstract Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array ), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, OR G-allele = 1.13, P meta = 1.60 × 10 −8 ). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.