The chromatin remodeler Snf2h is essential for oocyte meiotic cell cycle progression

Oocytes are indispensable for mammalian life. Thus, it is important to understand how mature oocytes are generated. As a critical stage of oocytes development, meiosis has been extensively studied, yet how chromatin remodeling contributes to this process is largely unknown. Here, we demonstrate that the ATP-dependent chromatin remodeling factor Snf2h (also known as Smarca5) plays a critical role in regulating meiotic cell cycle progression. Females with oocyte-specific depletion of Snf2h are infertile and oocytes lacking Snf2h fail to undergo meiotic resumption. Mechanistically, depletion of Snf2h results in dysregulation of meiosis-related genes, which causes failure of maturation-promoting factor (MPF) activation. ATAC-seq analysis in oocytes revealed that Snf2h regulates transcription of a key meiotic gene, Prkar2b, by increasing its promoter chromatin accessibility. Our studies thus not only demonstrate the importance of Snf2h in oocyte meiotic resumption, but also reveal the mechanism underlying how a chromatin remodeling factor can regulate oocyte meiosis. RNA-seq were performed for Snf2h WT and KO oocytes at different developmental stages [i.e., Growing1 (40-45um), Growing2 (50-55um), Fully-grown oocytes (>70um)]. For each stage, two RNA-seq replicates were performed for each group. For FGO, oocytes were collected without or with prior hormon stimulation, which are referred to as non-hormone stimulated FGO (nFGO) and FGO, respectively. Two ATAC-seq replicates were performed in Growing1 and fully grown oocytes from both Snf2h WT and conditional KO female mice.