RT Journal Article
SR Electronic
T1 Functional analysis and co-evolutionary model of chromatin and DNA methylation networks in embryonic stem cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 008821
DO 10.1101/008821
A1 Enrique Carrillo de Santa Pau
A1 Juliane Perner
A1 David Juan
A1 Simone Marsili
A1 David Ochoa
A1 Ho-Ryun Chung
A1 Daniel Rico
A1 Martin Vingron
A1 Alfonso Valencia
YR 2014
UL http://biorxiv.org/content/early/2014/09/06/008821.abstract
AB We have analyzed publicly available epigenomic data of mouse embryonic stem cells (ESCs) combining diverse next-generation sequencing (NGS) studies (139 experiments from 30 datasets with a total of 77 epigenomic features) into a homogeneous dataset comprising various cytosine modifications (5mC, 5hmC and 5fC), histone marks and Chromatin related Proteins (CrPs). We applied a set of newly developed statistical analysis methods with the goal of understanding the associations between chromatin states, detecting co-occurrence of DNA-protein binding and epigenetic modification events, as well as detecting coevolution of core CrPs. The resulting networks reveal the complex relations between cytosine modifications and protein complexes and their dependence on defined ESC chromatin contexts.A detailed analysis allows us to detect proteins associated to particular chromatin states whose functions are related to the different cytosine modifications, i.e. RYBP with 5fC and 5hmC, NIPBL with 5hmC and OGT with 5hmC. Moreover, in a co-evolutionary analysis suggesting a central role of the Cohesin complex in the evolution of the epigenomic network, as well as strong co-evolutionary links between proteins that co-locate in the ESC epigenome with DNA methylation (MBD2 and CBX3) and hydroxymethylation (TET1 and KDM2A).In summary, the new application of computational methodologies reveals the complex network of relations between cytosine modifications and epigenomic players that is essential in shaping the molecular state of ESCs.