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

Abstract:

: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.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Rahjouei A,Pirouz M,Di Virgilio M,Kamin D,Kessel M

doi

10.1016/j.stemcr.2017.02.011

subject

Has Abstract

pub_date

2017-04-11 00:00:00

pages

813-821

issue

4

issn

2213-6711

pii

S2213-6711(17)30078-4

journal_volume

8

pub_type

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