DNA Demethylation Dynamics in the Human Prenatal Germline.

DNA Demethylation Dynamics in the Human Prenatal Germline.
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DOI:
10.1016/j.cell.2015.05.012
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发表时间:
2015-06-04
期刊:
影响因子:
64.5
通讯作者:
Clark AT
Clark AT
中科院分区:
生物学1区
文献类型:
--
作者:
Gkountela S;Zhang KX;Shafiq TA;Liao WW;Hargan-Calvopiña J;Chen PY;Clark AT

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人类的整体DNA去甲基化是发生在植入前胚胎和回复到幼稚基态多能干细胞(PSC)的基本过程。然而,人类生殖细胞中DNA甲基化重编程的程度是未知的。在这里,我们进行了全基因组亚硫酸氢盐测序(WGBS)和RNA测序(RNA-Seq)的人产前生殖系细胞从53-137天的发展。我们发现人类生殖细胞的转录组和甲基化组与人类PSC和人类囊胚的内细胞团(ICM)不同。利用这一资源来监测全球DNA去甲基化的结果,并将引发的PSC恢复到初始基态,我们发现了转座子处超低甲基化的热点,这些转座子在生殖系和ICM中受到保护,不受去甲基化的影响。总之,人类生殖系作为一种有价值的体内工具,用于监测从全球DNA去甲基化事件中出现的细胞的表观基因组。
Global DNA demethylation in humans is a fundamental process that occurs in pre-implantation embryos and reversion to naïve ground state pluripotent stem cells (PSCs). However the extent of DNA methylation reprogramming in human germline cells is unknown. Here we performed whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-Seq) of human prenatal germline cells from 53–137 days of development. We discovered that the transcriptome and methylome of human germline is distinct from both human PSCs and the inner cell mass (ICM) of human blastocysts. Using this resource to monitor the outcome of global DNA demethylation with reversion of primed PSCs to the naïve ground state, we uncovered hotspots of ultralow methylation at transposons that are protected from demethylation in the germline and ICM. Taken together the human germline serves as a valuable in vivo tool for monitoring the epigenome of cells that have emerged from a global DNA demethylation event.
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