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          Institute: MPI für molekulare Genetik     Collection: Sequencing Group     Display Documents



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ID: 536142.0, MPI für molekulare Genetik / Sequencing Group
Dynamic link of DNA demethylation, DNA strand breaks and repair in mouse zygotes
Authors:Wossidlo, Mark; Arand, Julia; Sebastiano, Vittorio; Lepikhov, Konstantin; Boiani, Michele; Reinhardt, Richard; Schöler, Hans; Walter, Jörn
Language:English
Date of Publication (YYYY-MM-DD):2010-06-02
Title of Journal:EMBO Journal
Volume:29
Issue / Number:11
Start Page:1877
End Page:1888
Copyright:© 2010 European Molecular Biology Organization
Review Status:not specified
Audience:Experts Only
Abstract / Description:In mammalian zygotes, the 5-methyl-cytosine (5mC) content of paternal chromosomes is rapidly changed by a yet unknown but presumably active enzymatic mechanism. Here, we describe the developmental dynamics and parental asymmetries of DNA methylation in relation to the presence of DNA strand breaks, DNA repair markers and a precise timing of zygotic DNA replication. The analysis shows that distinct pre-replicative (active) and replicative (active and passive) phases of DNA demethylation can be observed. These phases of DNA demethylation are concomitant with the appearance of DNA strand breaks and DNA repair markers such as γH2A.X and PARP-1, respectively. The same correlations are found in cloned embryos obtained after somatic cell nuclear transfer. Together, the data suggest that (1) DNA-methylation reprogramming is more complex and extended as anticipated earlier and (2) the DNA demethylation, particularly the rapid loss of 5mC in paternal DNA, is likely to be linked to DNA repair mechanisms.
Free Keywords:γH2A.X; DNA demethylation; DNA repair; epigenetic reprogramming; mouse zygote
Comment of the Author/Creator:E-mail: j.walter@mx.uni-saarland.de
External Publication Status:published
Document Type:Article
Communicated by:Richard Reinhardt
Affiliations:MPI für molekulare Genetik
External Affiliations:Department of Genetics/Epigenetics, Campus Saarbrücken, Saarland University, Saarbrücken, Germany
Max-Planck-Institut für Molekulare Biomedizin, Münster, Germany
Identifiers:DOI:10.1038/emboj.2010.80
ISSN:0261-4189
URL:http://www.nature.com/emboj/journal/v29/n11/pdf/em...
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