EED is Required for Male and Female Primordial Germ Cell Differentiation in the Embryonic Gonad

Primordial germ cells (PGCs) are the source of the entire germ line in adult animals. During PGC development in mammals, major epigenetic remodeling occurs characterized by an almost complete loss of DNA methylation from genomic DNA accompanied by a global increase in H3K27me3. Through the use of a conditional knockout in mouse PGCs (mPGCs), we show that H3K27me3 is essential for regulating the expression of germ cell differentiation genes and preventing precocious sex-specific differentiation in response to signals from the gonadal niche. Although H3K27me3 affects both male and female mPGC development during the gonadal stages of germline reprogramming in the embryo, the female germline is more sensitive to loss of H3K27me3. Taken together, the differentiation of mPGCs requires the coordinated activity of H3K27me3, DNA methylation and hydroxymethylation as well as the ubiquitination of H2AK119ub1 to regulate timing of PGC differentiation into oocytes and prospermatogonia.