EED is required for mouse primordial germ cell differentiation in the embryonic gonad

Development of primordial germ cells (PGCs) is required for reproduction. During PGC development in mammals, major epigenetic remodeling occurs, which is hypothesized to establish an epigenetic landscape for sex-specific germ cell differentiation and gametogenesis. In order to address the role of embryonic ectoderm development (EED) and histone 3 lysine 27 trimethylation (H3K27me3) in this process, we created an EED conditional knockout mouse and show that EED is essential for regulating the timing of sex-specific PGC differentiation in both ovaries and testes, as well as X chromosome dosage decompensation in testes. Integrating chromatin and whole genome bisulfite sequencing of epiblast and PGCs, we identified a poised repressive signature of H3K27me3/DNA methylation that we propose is established in the epiblast where EED and DNMT1 interact. Thus, EED joins DNMT1 in regulating the timing of sex-specific PGC differentiation during the critical window when the gonadal niche cells specialize into an ovary or testis.

Automated summary

The development of primordial germ cells (PGCs) is essential for reproduction. This study explores the role of embryonic ectoderm development (EED) and histone 3 lysine 27 trimethylation (H3K27me3) in sex-specific PGC differentiation. The findings suggest that EED plays a critical role in regulating the timing of sex-specific PGC differentiation and X chromosome dosage compensation in both ovaries and testes.