MEIOC prevents continued mitotic cycling and promotes meiotic entry during mouse oogenesis

To generate haploid gametes, germ cells must transition from mitosis to meiosis. In mammals, the transcriptional activator STRA8-MEIOSIN mediates the decision to enter the meiotic cell cycle, but how germ cells prevent continued mitotic cycling before meiotic entry remains unclear. MEIOC was previously shown to repress the mitotic program after meiotic entry. Here, we investigate the role of MEIOC in the mitosis-to-meiosis transition during mouse oogenesis. Using cell proliferation analysis and cell cycle transcriptomics, we demonstrate that MEIOC prevents continued mitotic cycling prior to meiotic entry in oogenic cells. We find that G1/S cyclin CCNA2 is downregulated during the mitosis-to-meiosis transition, and MEIOC contributes to this downregulation. MEIOC also promotes entry into meiosis by increasing Meiosin transcript abundance and consequently activating STRA8-MEIOSIN. Thus, in mouse oogenic cells, the transition from mitosis to meiosis occurs as two molecularly regulated steps - (1) the halt of mitotic cycling and (2) entry into the meiotic cell cycle - and that MEIOC modifies the cell cycle program to facilitate both steps in this transition.