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  Polycomb Binding Precedes Early-Life Stress Responsive DNA Methylation at the Avp Enhancer

Murgatroyd, C., & Spengler, D. (2014). Polycomb Binding Precedes Early-Life Stress Responsive DNA Methylation at the Avp Enhancer. PLOS ONE, 9(3): e90277. doi:10.1371/journal.pone.0090277.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0026-A5DD-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0026-A5DE-7
Genre: Journal Article

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journal.pone.0090277.pdf (Any fulltext), 647KB
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Murgatroyd, Chris1, Author
Spengler, Dietmar2, Author              
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1external, ou_persistent22              
2Dept. Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035295              

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 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.

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Language(s): eng - English
 Dates: 2014-03-05
 Publication Status: Published online
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Title: PLOS ONE
Source Genre: Journal
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Publ. Info: Cambridge, UK : PLOS ONE
Pages: - Volume / Issue: 9 (3) Sequence Number: e90277 Start / End Page: - Identifier: ISSN: 1932-6203