H3K9me2 is a determinant for the mitosis-to-meiosis transition in female germ cells

The transition from mitosis to meiosis is crucial for determining the germ cell fate and ensuring the successive production of gametes. However, the mechanisms underlying meiotic entry within the dynamic chromatin context still remain poorly understood. Herein, we demonstrate that H3K9me2, a key marker of heterochromatin formation, plays a pivotal role in the transition from mitosis to meiosis in female germ cells of mice. We show that H3K9me2 maintains high levels in female germ cells from embryonic day 13.5 to 15.5, which closely corresponds to the timing of entry into meiosis in female mice. Interestingly, the reduction of H3K9me2 levels impairs the transition from pluripotency to meiosis in female germ cells, and the role of H3K9me2 appears to act upstream of Stra8 and Dazl. Mechanistically, the multi-omics sequencing analyses of sorted germ cells reveal that H3K9me2 is specifically enriched at the promoter region of pluripotency transcription factor SOX2 and components of the ATP-dependent chromatin remodeling complex. Reduction of H3K9me2 levels results in increased chromatin accessibility, specifically for the pluripotent factor and ATP-dependent chromatin remodelers, thereby impeding the complete exit from the pluripotency progression. Hence, our findings highlight the essential role of H3K9me2 in controlling the exit from the pluripotent state and coordinating the competency of female germ cells, thereby indicating the fundamental role of chromatin remodeling processes in mitosis-to-meiosis transition. This study will provide new insights into the role of chromatin remodeling in the process of gamete production from stem cell to germ cell in vitro.