Epigenetic Reprogramming in Mouse Primordial Germ Cells

Jörn Walter
University of Saarland

Germ cells have the unique ability to reprogram the genome, which includes erasure of the parental imprints and epimutations, as well as the reactivation of the X chromosome. However, the precise timing, particularly of the early events, is unknown. Here, we report on the epigenetic changes in primordial germ cells (PGCs) between 10.5-13.5 dpc, and show that there is rapid demethylation of imprinted genes and other single copy loci, while repetitive elements undergo protracted and incomplete demethylation. We propose that this demethylation process, which occurs at the same time in primordial germ cells (PGCs) of both female and male embryos, is initiated upon entry of germ cells into the gonadal anlagen. The signal(s) triggering this reprogramming event in germ cells may originate from somatic cells of the bipotential immature gonads. This timing of the onset of reprogramming in PGCs is crucial since it ensures that germ cells acquire an equivalent epigenetic state prior to the differentiation of the definitive male and female gonads where new parental imprints are initiated subsequently. By contrast, the delayed and incomplete erasure of methylation in repetitive elements we observed may be essential for chromosomal stability and for preventing activation of transposons in order to reduce the risk of mutations.