DNA methylation changes during preimplantation development reveal inter species-differences and reprogramming events at imprinted genes [RNA-Seq]

Preimplantation embryos experience profound resetting of epigenetic information. Genome-wide analysis at single-base resolution had shown relevant species differences between human and mouse preimplantation embryos. Thus, we have extended such analysis to two key livestock species, the pig and the cow. We generated data showing the genome-wide DNA methylation landscape and whole-transcriptomes from gametes to blastocysts in both species. Detailed analysis revealed species specific differences and new insights in biological paradigms. An oocyte-like pattern of methylation in the cleavage stages, albeit with some reduction in methylation level, appears to persist even in cow blastocysts. Hypermethylated domains were prevalent over hypomethylated domains in pigs and cows, similar to human, while in the mouse the pattern is reversed. Interestingly, the behaviour of the oocyte hypo-domains in cleavage embryos revealed a complex dynamic of methylation reprogramming. It shows a pronounced increase in methylation at the 8-16 cell stage in pigs, similar to human, concomitant with ZFP57 expression. Even it is widely accepted that imprinted genes are established in the parental germline and robustly maintained through early development, our data show a greater dynamic of methylation in germline differentially methylated regions and few appear to maintain the expected 50% methylation from the 2-4 cell stage to blastocyst stage. It reveals that an active period of imprint stabilization until the blastocyst stage is required