CAS Key Laboratory of Genome Sciences and Information, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Cell. 2014 May 8;157(4):979-991. doi: 10.1016/j.cell.2014.04.017.
The reprogramming of parental methylomes is essential for embryonic development. In mammals, paternal 5-methylcytosines (5mCs) have been proposed to be actively converted to oxidized bases. These paternal oxidized bases and maternal 5mCs are believed to be passively diluted by cell divisions. By generating single-base resolution, allele-specific DNA methylomes from mouse gametes, early embryos, and primordial germ cell (PGC), as well as single-base-resolution maps of oxidized cytosine bases for early embryos, we report the existence of 5hmC and 5fC in both maternal and paternal genomes and find that 5mC or its oxidized derivatives, at the majority of demethylated CpGs, are converted to unmodified cytosines independent of passive dilution from gametes to four-cell embryos. Therefore, we conclude that paternal methylome and at least a significant proportion of maternal methylome go through active demethylation during embryonic development. Additionally, all the known imprinting control regions (ICRs) were classified into germ-line or somatic ICRs.
亲本甲基化组的重编程对于胚胎发育至关重要。在哺乳动物中，已经提出了父本 5-甲基胞嘧啶（5mC）被主动转化为氧化碱基。这些父本氧化碱基和母本 5mC 被认为通过细胞分裂被动稀释。通过生成来自小鼠配子、早期胚胎和原始生殖细胞（PGC）的单碱基分辨率的等位基因特异性 DNA 甲基化组，以及早期胚胎中氧化胞嘧啶碱基的单碱基分辨率图谱，我们报告了在母本和父本基因组中存在 5hmC 和 5fC，并发现大多数去甲基化 CpG 处的 5mC 或其氧化衍生物独立于从配子到四细胞胚胎的被动稀释而转化为未修饰的胞嘧啶。因此，我们得出结论，父本甲基化组和至少很大一部分母本甲基化组在胚胎发育过程中经历了主动去甲基化。此外，所有已知的印迹控制区（ICR）都被分类为生殖系或体细胞 ICR。
