Institute of Molecular Genetics, UMR 5535, Université Montpellier 2, Université Montpellier 1, CNRS, 34293 Montpellier Cedex 5, France.
Genome Res. 2012 Apr;22(4):633-41. doi: 10.1101/gr.130997.111. Epub 2012 Feb 22.
Epigenetic reprogramming, characterized by loss of cytosine methylation and histone modifications, occurs during mammalian development in primordial germ cells (PGCs), yet the targets and kinetics of this process are poorly characterized. Here we provide a map of cytosine methylation on a large portion of the genome in developing male and female PGCs isolated from mouse embryos. We show that DNA methylation erasure is global and affects genes of various biological functions. We also reveal complex kinetics of demethylation that are initiated at most genes in early PGC precursors around embryonic day 8.0-9.0. In addition, besides intracisternal A-particles (IAPs), we identify rare LTR-ERV1 retroelements and single-copy sequences that resist global methylation erasure in PGCs as well as in preimplantation embryos. Our data provide important insights into the targets and dynamics of DNA methylation reprogramming in mammalian germ cells.
表观遗传重编程的特征是胞嘧啶甲基化和组蛋白修饰的丧失，发生在哺乳动物发育中的原始生殖细胞（PGCs）中，但这个过程的靶点和动力学特征还不清楚。在这里，我们提供了一张在从胚胎小鼠中分离出的雄性和雌性 PGC 发育过程中基因组的大部分区域的胞嘧啶甲基化图谱。我们发现，DNA 甲基化的消除是全局性的，影响了各种生物学功能的基因。我们还揭示了早期 PGC 前体中大多数基因在胚胎第 8.0-9.0 天左右开始的去甲基化的复杂动力学。此外，除了内体 A 粒子（IAPs）之外，我们还发现了罕见的 LTR-ERV1 反转录元件和单拷贝序列，它们在 PGC 以及植入前胚胎中抵抗全局甲基化消除。我们的数据为哺乳动物生殖细胞中 DNA 甲基化重编程的靶点和动力学提供了重要的见解。
