MSL3 coordinates a transcriptional and translational meiotic program in female Drosophila

SummaryGamete formation from germline stem cells (GSCs) is essential for sexual reproduction. However, the regulation of GSC differentiation and meiotic entry are incompletely understood. Set2, which deposits H3K36me3 modifications, is required for differentiation of GSCs duringDrosophilaoogenesis. We discovered that the H3K36me3 reader Male-specific lethal 3 (MSL3) and the histone acetyltransferase complex Ada2a-containing (ATAC) cooperate with Set2 to regulate entry into meiosis in femaleDrosophila. MSL3 expression is restricted to the mitotic and early meiotic stages of the female germline, where it promotes transcription of genes encoding synaptonemal complex components and a germline enrichedribosomal protein S19paralog,RpS19b.RpS19bupregulation is required for translation of Rbfox1, a known meiotic cell cycle entry factor. Thus, MSL3 is a master regulator of meiosis, coordinating the expression of factors required for recombination and GSC differentiation. We find that MSL3 is expressed during mouse spermatogenesis, suggesting a conserved function during meiosis.