An essential role for a mammalian SWI/SNF chromatin-remodeling complex during male meiosis
An essential role for a mammalian SWI/SNF chromatin-remodeling complex during male meiosis
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DOI：
10.1242/dev.073478
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发表时间：
2012-03-15
期刊：
影响因子：
4.6
通讯作者：
Magnuson, Terry
中科院分区：
文献类型：
--
作者：
Kim, Yuna;Fedoriw, Andrew M.;Magnuson, Terry
生殖细胞发育和配子发生需要表观遗传修饰和染色质结构的全基因组转变。这些变化包括DNA和组蛋白的共价修饰以及重塑活动。在这里，我们利用atp酶亚基的一个条件等位基因——brahma相关基因1 (Brg1或Smarca4)，探讨了哺乳动物SWI/SNF染色质重塑复合体在精子发生过程中的作用。BRG1水平不仅在减数分裂早期达到峰值，在小鼠胚胎性腺细胞中BRG1的基因消融导致减数分裂i前期的停滞。与减数分裂停滞的时间一致，突变的精母细胞积累未修复的DNA并不能完成突触。此外，突变的精母细胞表现出组蛋白修饰和染色质结构的整体改变，表明基因组的异色性更强。总之，这些数据表明BRG1活性在精子发生过程中是必需的，并提示哺乳动物SWI/SNF复合体在减数分裂过程中发生的程序性重组和修复事件中发挥作用。
Germ cell development and gametogenesis require genome-wide transitions in epigenetic modifications and chromatin structure. These changes include covalent modifications to the DNA and histones as well as remodeling activities. Here, we explore the role of the mammalian SWI/SNF chromatin-remodeling complex during spermatogenesis using a conditional allele of the ATPase subunit, brahma-related gene 1 (Brg1, or Smarca4). Not only do BRG1 levels peak during the early stages of meiosis, genetic ablation of Brg1 in murine embryonic gonocytes results in arrest during prophase of meiosis I. Coincident with the timing of meiotic arrest, mutant spermatocytes accumulate unrepaired DNA and fail to complete synapsis. Furthermore, mutant spermatocytes show global alterations to histone modifications and chromatin structure indicative of a more heterochromatic genome. Together, these data demonstrate a requirement for BRG1 activity in spermatogenesis, and suggest a role for the mammalian SWI/SNF complex in programmed recombination and repair events that take place during meiosis.