| 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 |
2014-1-1
|
| 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*
DNA Methyltransferase 3A
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 |
2.74
|
| Times Cited |
25
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
Rx-GFP K/I EB5(AES0145) |
