作者
Joseph Hargan-Calvopina, Sara Taylor, Helene Cook, Zhongxun Hu, Serena A Lee, Ming-Ren Yen, Yih-Shien Chiang, Pao-Yang Chen, Amander T Clark
发表日期
2016/10/10
期刊
Developmental Cell
卷号
39
期号
1
页码范围
75-86
出版商
Elsevier
简介
Remodeling DNA methylation in mammalian genomes can be global, as seen in preimplantation embryos and primordial germ cells (PGCs), or locus specific, which can regulate neighboring gene expression. In PGCs, global and locus-specific DNA demethylation occur in sequential stages, with an initial global decrease in methylated cytosines (stage I) followed by a Tet methylcytosine dioxygenase (Tet)-dependent decrease in methylated cytosines that act at imprinting control regions (ICRs) and meiotic genes (stage II). The purpose of the two-stage mechanism is unclear. Here we show that Dnmt1 preserves DNA methylation through stage I at ICRs and meiotic gene promoters and is required for the pericentromeric enrichment of 5hmC. We discovered that the functional consequence of abrogating two-stage DNA demethylation in PGCs was precocious germline differentiation leading to hypogonadism and …
引用总数
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