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

被引:230
作者
Kagiwada, Saya [1 ]
Kurimoto, Kazuki [1 ,2 ]
Hirota, Takayuki [1 ,2 ]
Yamaji, Masashi [1 ,2 ]
Saitou, Mitinori [1 ,2 ,3 ,4 ]
机构
[1] Kyoto Univ, Grad Sch Med, Dept Anat & Cell Biol, Kyoto 6068501, Japan
[2] JST, ERATO, Kyoto, Japan
[3] Kyoto Univ, Ctr iPS Cell Res & Applicat, Kyoto 6068501, Japan
[4] Kyoto Univ, Inst Integrated Cell Mat Sci, Kyoto 6068501, Japan
关键词
cell cycle; chromatin dynamics; genome imprints; primordial germ cells; replication-coupled DNA; demethylation; PRIMORDIAL GERM-CELLS; EPIGENETIC INHERITANCE; CDNA AMPLIFICATION; DYNAMICS; SPECIFICATION; METHYLATION; 5-METHYLCYTOSINE; EXPRESSION; GENE; CHROMATIN;
D O I
10.1038/emboj.2012.331
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:340 / 353
页数:14
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