ECCB 2016 main conference Proteins

HT14 – Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs


Mississippi September 6, 2016 2:40 pm - 3:00 pm

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Highlight talk – Theme: Proteins

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.

Authors

David Juan, Spanish National Cancer Research Centre (CNIO), Spain
Juliane Perner, Max Planck Institute for Molecular Genetics, Germany
Enrique Carrillo-De Santa Pau, Spanish National Cancer Centre, Spain
Simone Marsili, Spanish National Cancer Research Centre (CNIO), Spain
David Ochoa, European Bioinformatics Institute (EMBL-EBI), United Kingdom
Ho-Ryun Chung, Max-Plank-Instut f. Molelulare Genetik, Germany
Martin Vingron, Max Planck Institut fuer molekulare Genetik, Germany
Daniel Rico, Spanish National Cancer Research Center, CNIO, Spain
Alfonso Valencia, Spanish National Cancer Research Centre, Spain

Source of publication

2016, Cell Reports, 14, 1246–1257