Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Suite B305. 825 NE 13th street, Oklahoma City, OK, 73104, USA.
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Epigenetics Chromatin. 2022 May 14;15(1):16. doi: 10.1186/s13072-022-00448-5.
Testis development and sustained germ cell production in adults rely on the establishment and maintenance of spermatogonia stem cells and their proper differentiation into spermatocytes. Chromatin remodeling complexes regulate critical processes during gamete development by restricting or promoting accessibility of DNA repair and gene expression machineries to the chromatin. Here, we investigated the role of Chd4 and Chd3 catalytic subunits of the NURD complex during spermatogenesis. Germ cell-specific deletion of chd4 early in gametogenesis, but not chd3, resulted in arrested early gamete development due to failed cell survival of neonate undifferentiated spermatogonia stem cell population. Candidate assessment revealed that Chd4 controls expression of dmrt1 and its downstream target plzf, both described as prominent regulators of spermatogonia stem cell maintenance. Our results show the requirement of Chd4 in mammalian gametogenesis pointing to functions in gene expression early in the process.
睾丸的发育和成年后持续的生殖细胞产生依赖于精原干细胞的建立和维持,以及它们向精母细胞的适当分化。染色质重塑复合物通过限制或促进 DNA 修复和基因表达机器对染色质的可及性,来调节配子发生过程中的关键过程。在这里,我们研究了 NURD 复合物的 Chd4 和 Chd3 催化亚基在精子发生中的作用。在配子发生早期,特异性敲除 chd4,但不敲除 chd3,会导致早期配子发育停滞,原因是新生未分化的精原干细胞群体的细胞存活失败。候选评估显示,Chd4 控制 dmrt1 及其下游靶基因 plzf 的表达,这两个基因都被描述为精原干细胞维持的重要调控因子。我们的研究结果表明 Chd4 在哺乳动物配子发生中是必需的,这表明它在早期的基因表达过程中发挥了作用。