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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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Chung,  H. R.
Computational Epigenetics (Ho-Ryun Chung), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Vingron,  M.
Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Juan, D., Perner, J., Carrillo de Santa Pau, E., Marsili, S., Ochoa, D., Chung, H. R., et al. (2016). Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs. Cell Reports, 14(5), 1246-1257. doi:10.1016/j.celrep.2016.01.008.


Cite as: https://hdl.handle.net/11858/00-001M-0000-002D-4760-2
Abstract
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.