De novo DNA methylation by Dnmt3a and Dnmt3b is dispensable for nuclear reprogramming of somatic cells to a pluripotent state

被引：87

作者：

Pawlak, Mathias ^{[1
]}

Jaenisch, Rudolf ^{[1
,2
]}

机构：

[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

来源：

GENES & DEVELOPMENT | 2011年 / 25卷 / 10期

关键词：

nuclear reprogramming; iPSCs; de novo DNA methylation; Dnmt3a; Dnmt3b; EMBRYONIC STEM-CELLS; IPS CELLS; METHYLTRANSFERASE DNMT3A; MAMMALIAN DEVELOPMENT; MOUSE; FIBROBLASTS; HYPOMETHYLATION; INACTIVATION; GENERATION; SYSTEM;

D O I：

10.1101/gad.2039011

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the transduction of defined transcription factors, and this process involves dynamic changes in DNA methylation. While the reprogramming of somatic cells is accompanied by demethylation of pluripotency genes, the functional importance of de novo DNA methylation has not been clarified. Here, using loss-of-function studies, we generated iPSCs from fibroblasts that were deficient in de novo DNA methylation mediated by Dnmt3a and Dnmt3b. These iPSCs reactivated pluripotency genes, underwent self-renewal, and showed restricted developmental potential that was rescued upon reintroduction of Dnmt3a and Dnmt3b. We conclude that de novo DNA methylation by Dnmt3a and Dnmt3b is dispensable for nuclear reprogramming of somatic cells.

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收藏

页码：1035 / 1040

页数：6

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