Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK.
Mol Cell. 2012 Dec 28;48(6):849-62. doi: 10.1016/j.molcel.2012.11.001. Epub 2012 Dec 6.
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.
基因组范围的 DNA 甲基化重编程发生在小鼠原始生殖细胞（PGCs）和胚胎植入前，但确切的动力学和生物学结果在很大程度上尚不清楚。我们已经对从 E6.5 上胚层到 E16.5 PGC 的关键阶段进行了全基因组亚硫酸氢盐测序（BS-Seq）和 RNA-Seq。在 PGC 扩增和迁移过程中，整体甲基化丢失，有证据表明存在被动去甲基化，但携带长期表观遗传记忆的序列（印记、X 染色体上的 CpG 岛、生殖系特异性基因）仅在 PGC 进入性腺时才被去甲基化。尽管整体低甲基化，但 PGC 的转录谱受到严格控制，具有多能性网络的短暂表达，表明重编程和多能性是不可分割的。我们的研究结果为理解生殖系中多能性的表观遗传基础状态提供了一个框架。
