SWI/SNF chromatin remodeling complex is required for initiation of sex-dependent differentiation in mouse germ cell

Sexual reproduction system creates sex-dependent gametes, oocytes and sperm. In mammals, sexually dimorphic differentiation commences in primordial germ cells (PGCs) in embryonic gonads; female PGCs differentiate to primary oocytes through entry into meiosis, but male PGCs differentiate to mitotically quiescent gonocytes where de novo DNA methylation takes place. Here we show that the transition from PGCs to female or male germ cells was abrogated in conditional knockout mice lacking Snf5 gene (Snf5 CKO mice), encoding a core subunit of SWI/SNF chromatin remodeling complex. In female mutant mice, the failure to upregulate meiosis-related genes resulted in impaired meiotic entry and progression, including defects in synapsis formation and DNA repair. In mutant males, entry to mitotic arrest was delayed, and de novo DNA-methylation-related genes were not upregulated, leading to hypomethylation in retrotransposons and imprinted genes. Collectively, our results demonstrate that SWI/SNF chromatin remodeling complex is required for transcriptional reprogramming in initiation of sex-dependent differentiation of germ cells.//