Programming and inheritance of parental DNA methylomes in mammals.

Programming and inheritance of parental DNA methylomes in mammals.
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哺乳动物亲本 DNA 甲基化组的编程和遗传

DOI:
10.1016/j.cell.2014.04.017
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发表时间:
2014-05-08
期刊:
影响因子:
64.5
通讯作者:
Liu J
Liu J
中科院分区:
生物学1区
文献类型:
--
作者:
Wang L;Zhang J;Duan J;Gao X;Zhu W;Lu X;Yang L;Zhang J;Li G;Ci W;Li W;Zhou Q;Aluru N;Tang F;He C;Huang X;Liu J

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亲本甲基组的重编程对胚胎发育至关重要。在哺乳动物中,父本5-甲基胞嘧啶(5mCs)被认为是主动转化为氧化碱基。这些父亲的氧化碱基和母亲的5mc被认为是被动地被细胞分裂稀释。通过从小鼠配子、早期胚胎和原始生殖细胞(PGC)中生成单碱基分辨率的等位基因特异性DNA甲基组,以及早期胚胎氧化胞嘧啶碱基的单碱基分辨率图,我们报告了5hmC和5fC在母体和父亲基因组中的存在,并发现5mC或其氧化衍生物,在大多数去甲基化的CpGs中,被转化为未修饰的胞嘧啶,而不依赖于配子到4细胞胚胎的被动稀释。因此,我们得出结论,在胚胎发育过程中,父本甲基化组和至少相当大比例的母本甲基化组经历了活跃的去甲基化。此外,所有已知的印迹控制区(ICRs)被划分为种系或体细胞ICRs。
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 4-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.
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