Re-establishment of H3K9me2 eliminates the transcriptional inhibition of ST18 on meiotic genes and orchestrates female germ cell development

Abstract Epigenetic reprogramming is widespread and highly active during gametogenesis, which is usually involving in the expression of critical genes. The expression of genes couple with transcription activation, and the transcriptional regulation by transcription factors predetermine protein translation for biological processes. In this study, we found that EHMT1-mediated re-establishment of H3K9me2 played crucial roles in the progression of meiosis in female germ cells. EHMT1 deficient female mice were nearly infertile due to the arrest of zygotene in embryonic germ cells, which was caused by downregulated expression of key meiotic genes. Furthermore, we identified transcription suppressor, particularly ST18, for meiotic genes by combining RNA-seq, Cut&Tag seq analysis, and luciferase reporter assays. We uncovered that H3K9me2 mediated ST18 expression homeostasis and played critical roles in regulating the timed expression of key meiotic genes. Overall, we revealed that EHMT1-mediated H3K9me2 re-establishment facilitated the expression of key meiotic genes for female meiosis progression.