GSE120994
CFP1 safeguards male meiotic progression by regulating meiotic gene expression
Meiosis occurs specifically in germ cells to produce sperm and oocytes that are competent for sexual reproduction. Multiple factors are required for successful meiotic entry, progression, and termination. Trimethylation of histone H3 on lysine 4 (H3K4me3), a mark of active transcription, has been implicated in spermatogenesis by forming double strand breaks (DSBs). The role of H3K4me in transcriptional regulation during meiosis however, remains poorly understood. Here, we reveal that mouse CXXC finger protein 1 (Cfp1), a component of H3K4me methyltransferases Setd1a/b, is dynamically expressed in differentiating male germ cells and safeguards meiosis by controlling gene expression. Depletion of Cfp1 in male germ cells resulted in infertility with reduced H3K4me3, spermatogenic arrest, and repression of essential germ cell development and meiosis genes. Importantly, ChIP-Seq analysis revealed that Cfp1 is mainly enriched at transcriptional start sites to promote gene expression and H3K4me2/3 levels at pachytene stage. The most highly enriched genes were associated with meiosis and homologous recombination during differentiation of spermatocytes to round spermatids. Additionally, missense mutations of human CFP1 were prevalent in patients with nonobstructive azoospermia. Therefore, our study establishes a mechanistic link between CFP1-mediated transcriptional control and meiotic progression, and provides unprecedented genetic basis for understanding human sterility. Overall design: We performed ChIP-Seq (Cfp1 and H3K4me3) analysis in P21 mouse spermatocytes.