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Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs

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EpigenomicCo-localizationandCo-evolution_2016.pdf (2.57 MB)
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URI: http://hdl.handle.net/20.500.12105/7890
ISSN: 22111247
DOI: 10.1016/j.celrep.2016.01.008
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2016-02-09
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Cell Press
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Epigenetic communication through histone and cytosine modifications is essential for gene regulation and cell identity. Here, we propose a framework that is based on a chromatin communication model to get insight on the function of epigenetic modifications in ESCs. The epigenetic communication network was inferred from genome-wide location data plus extensive manual annotation. Notably, we found that 5-hydroxymethylcytosine (5hmC) is the most-influential hub of this network, connecting DNA demethylation to nucleosome remodeling complexes and to key transcription factors of pluripotency. Moreover, an evolutionary analysis revealed a central role of 5hmC in the co-evolution of chromatin-related proteins. Further analysis of regions where 5hmC co-localizes with specific interactors shows that each interaction points to chromatin remodeling, stemness, differentiation, or metabolism. Our results highlight the importance of cytosine modifications in the epigenetic communication of ESCs.
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5-Methylcytosine Animals Chromatin Cytosine Mice Mouse Embryonic Stem Cells Multiprotein Complexes Signal Transduction Epigenesis, Genetic Evolution, Molecular
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Cell Rep. 2016;14(5):1246-1257
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https://doi.org/10.1016/j.celrep.2016.01.008.
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journal article