Epigenetic Reprogramming in Primordial Germ Cells in Mice

抄録

Germline cells are the sole source of the transmission of genetic and epigenetic information to the next generation. Epigenetic information is reprogrammed during germ cell development to reacquire cellular totipotency and prevent the accumulation of epimutations. In this review, we summarize epigenetic reprogramming, in particular, DNA demethylation in developing primordial germ cells (PGCs). The recent development of next-generation sequencing, and the discovery of 5-methylcytosine oxidation are major breakthroughs in the study of epigenetic reprogramming in PGCs. DNA methylation analysis with high-throughput sequencing has uncovered the dynamics of DNA methylation erasure at single-locus resolution, which has revealed the global loss of DNA methylation in migrating PGCs, and locus-specific DNA demethylation in gonadal PGCs. The disruption of ten-eleven translocation genes shows that they are required for DNA demethylation at germline-specific genes in gonadal PGCs. These findings indicate that passive and active demethylation pathways operate synergistically and/or in parallel to ensure efficient global demethylation in developing PGCs.