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EMBO J. 2013 Feb 6;32(3):340-53. doi: 10.1038/emboj.2012.331. Epub 2012 Dec 14.

Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice.

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  • 1Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.


Genome-wide DNA demethylation, including the erasure of genome imprints, in primordial germ cells (PGCs) is a critical first step to creating a totipotent epigenome in the germ line. We show here that, contrary to the prevailing model emphasizing active DNA demethylation, imprint erasure in mouse PGCs occurs in a manner largely consistent with replication-coupled passive DNA demethylation: PGCs erase imprints during their rapid cycling with little de novo or maintenance DNA methylation potential and no apparent major chromatin alterations. Our findings necessitate the re-evaluation of and provide novel insights into the mechanism of genome-wide DNA demethylation in PGCs.

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