Juan, DavidPerner, JulianeCarrillo-de-Santa-Pau, EnriqueMarsili, SimoneOchoa, DavidChung, Ho-RyunVingron, MartinRico, DanielValencia, Alfonso2019-07-112019-07-112016-02-09Cell Rep. 2016;14(5):1246-125722111247http://hdl.handle.net/20.500.12105/7890Epigenetic 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.engVoRhttp://creativecommons.org/licenses/by-nc-sa/4.0/5-MethylcytosineAnimalsChromatinCytosineMiceMouse Embryonic Stem CellsMultiprotein ComplexesSignal TransductionEpigenesis, GeneticEvolution, MolecularAtribución-NoComercial-CompartirIgual 4.0 Internacional268324181451246-125710.1016/j.celrep.2016.01.0082211-1247Cell reportsopen access