The conservation and divergence of epigenitic reprogramming during mammalian early development

To explore how parental epigenetic information is transmitted to the next generation across mammals, we systematically investigated the epigenomes of oocytes and early embryos among human, bovine, porcine, rat, and mouse. This unprecedented dataset revealed strikingly diverse, species-specific innovation of epigenetic transition. In oocytes, DNA methylation is restricted to active gene bodies in rodents, allowing methylation of maternal imprints but not intergenic paternal imprints. Strikingly, hypermethylation also occurs in non-transcribed regions in porcine and bovine, where paternal imprints instead reside in hypomethylated, megabase-long “CpG continents (CGCs)”. Despite the presence of H3K4me3 and H3K27me3 domains in non-human oocytes, only rodent H3K27me3 survives beyond genome activation, supporting H3K27me3-mediated imprinting. Coincidently, regulatory elements are segregated away from H3K27me3 domains, the ectopic invasion of which leads to aberrant embryonic transcription. Finally, human does not fully resemble any of the rest species. Hence, mammals invent diverse epigenetic inheritance and reprogramming which center around a delicate balance in establishing imprints while protecting other regulatory regions.