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  MAD2L2 promotes open chromatin in embryonic stem cells and derepresses the Dppa3 locus.

Rahjouei, A., Pirouz, M., Di Virgilio, M., Kamin, D., & Kessel, M. (2017). MAD2L2 promotes open chromatin in embryonic stem cells and derepresses the Dppa3 locus. Stem Cell Reports, 8(4), 813-821. doi:10.1016/j.stemcr.2017.02.011.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-E9C9-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-0917-B
Genre: Journal Article

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 Creators:
Rahjouei, A.1, Author              
Pirouz, M.1, Author              
Di Virgilio, M., Author
Kamin, D.2, Author              
Kessel, M.1, Author              
Affiliations:
1Research Group of Developmental Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_578586              
2Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society, ou_578627              

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Free keywords: heterochromatin; epigenetics; germ cells; DNA damage; DNA methylation
 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.

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Language(s): eng - English
 Dates: 2017-03-16
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.stemcr.2017.02.011
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Title: Stem Cell Reports
Source Genre: Journal
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Pages: - Volume / Issue: 8 (4) Sequence Number: - Start / End Page: 813 - 821 Identifier: -