Programming and inheritance of parental DNA methylomes in mammals

Lu Wang, Jun Zhang, Jialei Duan, Xinxing Gao, Wei Zhu, Xingyu Lu, Lu Yang, Jing Zhang, Guoqiang Li, Weimin Ci, Wei Li, Qi Zhou, Neel Aluru, Fuchou Tang, Chuan He, Xingxu Huang, Jiang Liu

Research output: Contribution to journalArticlepeer-review

410 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)979-991
Number of pages13
JournalCell
Volume157
Issue number4
DOIs
StatePublished - May 8 2014
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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