KDM2A is essential for spermatogenesis and male fertilitly

Recent studies have shown that KDM2A acts as a lysine demethylase targeting H3K36me1/2 and plays essential role in modulating the chromatin structure. Herein, we demonstrate that Kdm2a deletion in pre-meiotic germ cells using Stra8GFP-Cre knock-in mice leads to complete sterility, with spermatogenesis ultimately arresting at the zygotene stage of meiosis. RNA sequencing (RNA-seq) reveals that Kdm2a can repress the expression of genes essential for spermatogonial development and facilitate expression of genes required for meiosis. Unexpectedly, our chromatin immunoprecipitation followed by sequencing (ChIP-seq) results indicate a special role of Kdm2a in the removal of H3K36me3 mark from its genomic target regions in male germ cells, suggesting that Kdm2a may act as a lysine demethylase toward H3K36me3 in spermatogenic cells different from its traditional functions in somatic cells. Furthermore, our findings reveal that KDM2A can recruit the transcription factor E2F1 and its co-factor HCFC1 to the promoters of key genes required for meiosis entry and progression.