e-space
Manchester Metropolitan University's Research Repository

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

    Murgatroyd, C and Spengler, D (2014) Polycomb Binding Precedes Early-Life Stress Responsive DNA Methylation at the Avp Enhancer. PLOS ONE, 9. ISSN 1932-6203

    [img]
    Preview

    Available under License Creative Commons Attribution.

    Download (661kB) | Preview

    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.

    Impact and Reach

    Statistics

    Activity Overview
    6 month trend
    190Downloads
    6 month trend
    311Hits

    Additional statistics for this dataset are available via IRStats2.

    Altmetric

    Actions (login required)

    View Item View Item