生物
重编程
DNA甲基化
外胚层
表观遗传学
生殖系
遗传学
亚硫酸氢盐测序
DNA去甲基化
RNA导向的DNA甲基化
甲基化
基因组
基因
胚胎干细胞
基因表达
原肠化
作者
Stefanie Seisenberger,Simon Andrews,Felix Krueger,Julia Arand,Joern Walter,Fátima Santos,Christian Popp,Bernard Thienpont,Wendy Dean,Wolf Reik
出处
期刊:Molecular Cell
[Elsevier]
日期:2012-12-01
卷期号:48 (6): 849-862
被引量:783
标识
DOI:10.1016/j.molcel.2012.11.001
摘要
Genome-wide DNA methylation reprogramming occurs in mouse primordial germ cells (PGCs) and preimplantation embryos, but the precise dynamics and biological outcomes are largely unknown. We have carried out whole-genome bisulfite sequencing (BS-Seq) and RNA-Seq across key stages from E6.5 epiblast to E16.5 PGCs. Global loss of methylation takes place during PGC expansion and migration with evidence for passive demethylation, but sequences that carry long-term epigenetic memory (imprints, CpG islands on the X chromosome, germline-specific genes) only become demethylated upon entry of PGCs into the gonads. The transcriptional profile of PGCs is tightly controlled despite global hypomethylation, with transient expression of the pluripotency network, suggesting that reprogramming and pluripotency are inextricably linked. Our results provide a framework for the understanding of the epigenetic ground state of pluripotency in the germline.
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