Department of Cell Biology, Yale University, New Haven, Connecticut, USA.
Biol Reprod. 2012 Jun 22;86(6):186. doi: 10.1095/biolreprod.111.097097. Print 2012 Jun.
Mammalian spermatogenesis is a complex process that involves spatiotemporal regulation of gene expression and meiotic recombination, both of which require the modulation of chromatin structure. Proteins important for chromatin regulation during spermatogenesis remain poorly understood. Here we addressed the role of BRG1, the catalytic subunit of the mammalian Swi/Snf-like BAF chromatin-remodeling complex, during spermatogenesis in mice. BRG1 expression is dynamically regulated in the male germline, being weakly detectable in spermatogonia, highly expressed in pachytene spermatocytes, and turned off in maturing round spermatids. This expression pattern overlaps that of Brm, the Brg1 homolog. While Brm knockout males are known to be fertile, germline-specific Brg1 deletion completely arrests spermatogenesis at the midpachytene stage, which is associated with spermatocyte apoptosis and apparently also with impaired homologous recombination and meiotic sex chromosome inactivation. However, Brg1 is dispensable for gammaH2AX formation during meiotic recombination, contrary to its reported role in DNA repair in somatic cells. Our study reveals the essential role of Brg1 in meiosis and underscores the differences in the mechanisms of DNA repair between germ cells and somatic cells.
哺乳动物精子发生是一个复杂的过程，涉及基因表达和减数分裂重组的时空调节，这两者都需要染色质结构的调节。在精子发生过程中，对于染色质调节很重要的蛋白质仍然知之甚少。在这里，我们研究了 BRG1 在小鼠精子发生中的作用，BRG1 是哺乳动物 Swi/Snf 样 BAF 染色质重塑复合物的催化亚基。BRG1 的表达在雄性生殖细胞中是动态调节的，在精原细胞中检测到弱表达，在粗线期精母细胞中高表达，在成熟的圆形精子中关闭。这种表达模式与 Brm 重叠，Brg1 的同源物。虽然 Brm 敲除雄性是可育的，但生殖细胞特异性 Brg1 缺失完全阻止了精子发生，处于粗线期中期，这与精母细胞凋亡明显相关，并且还与同源重组和减数分裂性染色体失活受损有关。然而，Brg1 对于减数分裂重组期间的 γH2AX 形成是可有可无的，这与它在体细胞中的 DNA 修复中的作用相反。我们的研究揭示了 Brg1 在减数分裂中的重要作用，并强调了生殖细胞和体细胞之间 DNA 修复机制的差异。
