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

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

Stem cell reports 2017 Apr 11

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The chromatin of naive embryonic stem cells (ESCs) has a largely open configuration, as evident by the lack of condensed heterochromatin and the hypomethylation of DNA. Several molecular mechanisms promoting this constellation were previously identified. Here we present evidence for an important epigenetic function of MAD2L2, a protein originally known for its role in DNA damage repair, and for its requirement in germ cell development. We demonstrate using super-resolution microscopy that numerous MAD2L2 microfoci are exclusively associated with euchromatin, similar to other factors of the DNA damage response. In the absence of MAD2L2 the amount of heterochromatin demarcated by H3K9me2 was significantly increased. Among the most strongly suppressed genes was Dppa3, an ESC- and germ-cell-specific gene regulating DNA methylation. In Mad2l2-deficient ESCs 5-methylcytosine levels were globally increased, while several imprinted genes became hypomethylated and transcriptionally activated. Our results emphasize the important function of MAD2L2 for the open chromatin configuration of ESCs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Ali Rahjouei, Mehdi Pirouz, Michela Di Virgilio, Dirk Kamin, Michael Kessel. MAD2L2 Promotes Open Chromatin in Embryonic Stem Cells and Derepresses the Dppa3 Locus. Stem cell reports. 2017 Apr 11;8(4):813-821