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.
Highlights
Intracellular and intercellular communication between proteins and/or other elements in the cell is essential for homeostasis and to respond to stimuli
Epigenetic communication through histone and cytosine modifications is essential for gene regulation and cell identity
We propose a framework that is based on a chromatin communication model to get insight on the function of epigenetic modifications in embryonic stem cells (ESCs)
Summary
5-hydroxymethylcytosine (5hmC) plays a key role in the epigenomic communication network of embryonic stem cells. Juan et al build a communication network based in colocalization of epigenomic data and literature. The analysis of the network and its components reveals that proteins reading and editing 5hmC co-evolve and serve as links between diverse molecular processes.
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