Epigenetic reprogramming during germline development

Following primordial germ cell (PGC) specification, global, as well as parent-specific, methylation marks are erased, to be subsequently re-established in a sex-dependent manner during gametogenesis. Identification of key regulators that participate in the global remodeling of the epigenome, together with genome-wide sequencing maps of the dynamic epigenome landscape from the post-implantation embryo through gametogenesis, significantly enhanced our understanding of these key events. Yet, a full understanding of the developmental timing, kinetics and mechanisms of these processes at different loci is still far from complete. Furthermore, as previous studies mostly applied bulk population sequencing approaches, the levels of cell-to-cell variations was not fully appreciated. We will utilize our allele-specific DNA methylation reporter systems to monitor sex-specific methylation erasure and establishment, at single cell resolution. Our unique experimental systems, which allow the monitoring and isolation of cells based on their epigenetic state, will enable prospective and mechanistic studies of locus-specific methylation and demethylation.