MAD2L2 Promotes Open Chromatin in Embryonic Stem Cells and Derepresses the Dppa3 Locus

作者: Ali Rahjouei , Mehdi Pirouz , Michela Di Virgilio , Dirk Kamin , Michael Kessel

DOI: 10.1016/J.STEMCR.2017.02.011

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摘要: The chromatin of naive embryonic stem cells (ESCs) has a largely open configuration, as evident by the lack condensed heterochromatin and hypomethylation DNA. Several molecular mechanisms promoting this constellation were previously identified. Here we present evidence for an important epigenetic function MAD2L2, protein originally known its role in DNA damage repair, requirement germ cell development. We demonstrate using super-resolution microscopy that numerous MAD2L2 microfoci are exclusively associated with euchromatin, similar to other factors response. In absence amount demarcated H3K9me2 was significantly increased. Among most strongly suppressed genes Dppa3, ESC- germ-cell-specific gene regulating methylation. Mad2l2-deficient ESCs 5-methylcytosine levels globally increased, while several imprinted became hypomethylated transcriptionally activated. Our results emphasize configuration ESCs.

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