Department of Biological Sciences/RNA Institute, University at Albany SUNY, Albany, NY 12202, USA.
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Development. 2022 Jan 1;149(1). doi: 10.1242/dev.199625. Epub 2022 Jan 4.
Gamete formation from germline stem cells (GSCs) is essential for sexual reproduction. However, the regulation of GSC differentiation is incompletely understood. Set2, which deposits H3K36me3 modifications, is required for GSC differentiation during Drosophila oogenesis. We discovered that the H3K36me3 reader Male-specific lethal 3 (Msl3) and histone acetyltransferase complex Ada2a-containing (ATAC) cooperate with Set2 to regulate GSC differentiation in female Drosophila. Msl3, acting independently of the rest of the male-specific lethal complex, promotes transcription of genes, including a germline-enriched ribosomal protein S19 paralog RpS19b. RpS19b upregulation is required for translation of RNA-binding Fox protein 1 (Rbfox1), a known meiotic cell cycle entry factor. Thus, Msl3 regulates GSC differentiation by modulating translation of a key factor that promotes transition to an oocyte fate.
生殖细胞（GSCs）从生殖细胞分化为配子对于有性生殖至关重要。然而，GSC 分化的调控机制尚不完全清楚。在果蝇卵子发生过程中，组蛋白 H3K36me3 修饰的沉积酶 Set2 对于 GSC 分化是必需的。我们发现，H3K36me3 阅读器 Male-specific lethal 3（Msl3）和含有组蛋白乙酰转移酶复合物 Ada2a 的复合物（ATAC）与 Set2 合作，调节雌性果蝇 GSC 的分化。Msl3 独立于其余雄性致死复合物发挥作用，促进包括一个富含生殖细胞的核糖体蛋白 S19 同源物 RpS19b 的基因转录。RpS19b 的上调对于 RNA 结合 Fox 蛋白 1（Rbfox1）的翻译是必需的，Rbfox1 是已知的减数分裂细胞周期进入因子。因此，Msl3 通过调节翻译一个关键因子来调节 GSC 分化，该因子促进向卵母细胞命运的转变。
