RRC ID 44948
Author Murgatroyd C, Spengler D.
Title Polycomb binding precedes early-life stress responsive DNA methylation at the Avp enhancer.
Journal PLoS ONE
Abstract Early-life stress (ELS) in mice causes sustained hypomethylation at the downstream Avp enhancer, subsequent overexpression of hypothalamic Avp and increased stress responsivity. The sequence of events leading to Avp enhancer methylation is presently unknown. Here, we used an embryonic stem cell-derived model of hypothalamic-like differentiation together with in vivo experiments to show that binding of polycomb complexes (PcG) preceded the emergence of ELS-responsive DNA methylation and correlated with gene silencing. At the same time, PcG occupancy associated with the presence of Tet proteins preventing DNA methylation. Early hypothalamic-like differentiation triggered PcG eviction, DNA-methyltransferase recruitment and enhancer methylation. Concurrently, binding of the Methyl-CpG-binding and repressor protein MeCP2 increased at the enhancer although Avp expression during later stages of differentiation and the perinatal period continued to increase. Overall, we provide evidence of a new role of PcG proteins in priming ELS-responsive DNA methylation at the Avp enhancer prior to epigenetic programming consistent with the idea that PcG proteins are part of a flexible silencing system during neuronal development.
Volume 9(3)
Pages e90277
Published 2014
DOI 10.1371/journal.pone.0090277
PII PONE-D-13-43228
PMID 24599304
PMC PMC3943912
MeSH Animals Arginine Vasopressin / genetics* Cell Differentiation Cell Line Chromatin / genetics Chromatin / metabolism DNA (Cytosine-5-)-Methyltransferases / metabolism DNA Methylation* Enhancer Elements, Genetic* Epigenesis, Genetic Gene Expression Histones / metabolism Hypothalamus / cytology Male Methyl-CpG-Binding Protein 2 / metabolism Mice, Inbred C57BL Mice, Transgenic Polycomb Repressive Complex 2 / metabolism Polycomb-Group Proteins / metabolism* Protein Binding Stress, Physiological*
IF 2.776
Times Cited 12
Human and Animal Cells