Reprogramming And Inheritance Of Parental DNA Methylomes In Mammals

DNA methylation is of significance in development. After fertilization, genome-wide demethylation occurs during mammalian early embryogenesis. DNA demethylation can take place actively or passively. Based on the results from cell immunostaining and reduced representation bisulphite sequencing (RRBS) data, it is previously believed that paternal DNA is actively demethylated followed by passive dilution of its oxidized derivatives, and maternal DNA is passively demethylated due to the absence of the methylation maintenance mechanism. However, the hypothesis may be inaccurate or partial because of the low resolution and the lack of allele-specific analyses.With single-base resolution, allele-specific DNA methylomes of gametes, early embryos and primordial germ cells, as well as single-base resolution maps of oxidized cytosines, the existence of 5-hydroxymethylcytosine and 5-formylcytosine in both maternal and paternal genomes is observed, suggesting that maternal genome may also undergo Tet-mediated active demethylation. Besides, it is indicated that from gametes to four-cell embryos, at the majority of demethylated CpGs, active demethylation is involved in the removal or modification of 5mC, and the demethylation is not mainly dependent on the passive dilution of the oxidized derivatives of 5mC. Thus, it is concluded that not only paternal methylome, but also at least a significant proportion of maternal genome undergoes active demethylation. Furthermore, all the known imprinting control regions (ICRs) are classified into germ-line ICRs or somatic ICRs.