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Cell Rep. 2016 Feb 9;14(5):1246-1257. doi: 10.1016/j.celrep.2016.01.008. Epub 2016 Jan 28.

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

Author information

1
Structural Biology and BioComputing Programme, Spanish National Cancer Research Center - CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain.
2
Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.
3
European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
4
Otto-Warburg-Laboratories Epigenomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.
5
Structural Biology and BioComputing Programme, Spanish National Cancer Research Center - CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain. Electronic address: drico@cnio.es.
6
Structural Biology and BioComputing Programme, Spanish National Cancer Research Center - CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain. Electronic address: valencia@cnio.es.

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.

PMID:
26832418
DOI:
10.1016/j.celrep.2016.01.008
[Indexed for MEDLINE]
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