Programming and Inheritance of Parental DNA Methylomes in Mammals

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. [Display omitted] •At least a significant proportion of maternal methylome is actively demethylated•5hmC and 5fC exist in both maternal and paternal genome•DNA demethylation is independent of the passive dilution of oxidized 5mC bases•Classification of all the known ICRs into germ-line ICRs or somatic ICRs Allele-specific, single-base-resolution sequencing of mouse early embryos shows that mammalian paternal methylome and a significant proportion of maternal methylome undergo active demethylation during early embryonic development.