Figure 2

The epigenetic genome-wide reprogramming cycle involves two phases of DNA erasure in the mouse (from [[91],[161],[162]]). (1) A first wave of DNA demethylation takes place in the male (blue curve) or female (red curve) primordial germ cells (PGC) of the F1 individuals; this occurs throughout the genome, including the imprinted genes (embryonic day (E10.5-13.5). (2) Then, the genome of the gametes undergoes de novo methylation, with maternal methylation marks established at a later stage (ovulation) than paternal marks (E14). (3) A second wave of DNA demethylation takes place after fertilization in the F2 zygote (E0.5), with a more rapid demethylation in the paternal than the maternal genome. However, the paternal and maternal imprinted genes maintain their methylation pattern throughout this preimplantation reprogramming (dotted curves), allowing the inheritance of parent-specific monoallelic expression in somatic tissues of the F2 individual. (4) Finally, genome-wide remethylation occurs in both parental genomes at about the time of implantation (E3.5). Altogether the very early embryonic development corresponds to an epigenomic reprogramming step, during which the new epigenetic marks are more prone to being impacted by the environment. This explains why the environment experienced during early development has a greater impact on the adult phenotype than that experienced later in life[163]. Moreover, the timing of the two global DNA demethylation and remethylation waves differs between male and female genomes, possibly explaining why they may be differently impacted by a stress applied during these stages[91, 164].