Transcription factor NFYA directs male meiotic entry by regulating accessible chromatin at meiotic promoters in mice

Meiotic prophase I, characterized by homologous recombination and synapsis, is a critical step in spermatogenesis. This process entails extensive changes to chromatin and transcription. Prior to prophase I, accessible chromatin bound by paused Pol II at meiotic gene promoters is essential for their timely activation later during meiosis. However, the factors responsible for establishing accessible chromatin at meiotic gene promoters before entry into prophase I are unknown. Here, we discovered that NFYA, expressed in pre-meiotic germ cells, regulates accessible chromatin at meiotic gene promoters, including those activated by the STRA8/MEISON axis. Concordantly, conditional germline deletion of Nfya in male mice blocks meiotic entry. Single-cell ATAC-seq analysis shows that loss of NFYA in pre-meiotic cells disrupts accessible chromatin at poised meiotic gene promoters. These findings establish NFYA as a regulator of accessible chromatin at meiotic gene promoters and of the timely activation of the meiotic genetic program.