Figure 4.

Transgenerational cycle of imprinting marks in mouse. Generational inheritance and epigenetic reprogramming occur through a cycle of erasure, establishment, and maintenance of imprinting marks as illustrated here by successive demethylation and methylation events in the paternal and maternal genome. All methylation marks are erased in primordial germ cells (PGCs) by a genome-wide methylation event between embryonic day 8 (E8) and E13.5. Next, the imprinting marks are established by de novo methylation starting first in the male germ cells around E14.5 and then in growing oocytes after birth. The established sex-specific imprints are maintained until the appearance of the next-generation PGCs; however, further epigenetic reprogramming events occur to direct embryonic development and tissue-specific gene expression in nonimprinted genes. While the paternal genome undergoes active demethylation at fertilization, the maternal genome is passively demethylated during successive cleavages of the early embryo. Finally, another de novo methylation takes place at the time of implantation.