H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation.
H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation.
复制标题
H2B 泛素化通过促进染色质松弛来调节减数分裂重组
DOI：
10.1093/nar/gkw652
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发表时间：
2016-11-16
影响因子：
14.9
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Xu Z;Song Z;Li G;Tu H;Liu W;Liu Y;Wang P;Wang Y;Cui X;Liu C;Shang Y;de Rooij DG;Gao F;Li W
减数分裂重组是大多数有性生殖物种的生育力所必需的，但这一过程的分子机制在哺乳动物中仍然知之甚少。在这里，我们表明RNF 20介导的H2 B泛素化是减数分裂重组所必需的。生殖细胞特异性敲除H2 B泛素化E3连接酶RNF 20导致完全男性不育。Stra 8-Rnf 20 −/−精母细胞由于受损的程序性双链断裂（DSB）修复而在粗线期停滞。进一步的研究表明，生殖细胞中RNF 20的耗尽会影响染色质松弛，从而阻止程序化的DSB修复因子被募集到染色质上的适当位置。H2 B泛素化缺陷细胞的配子发生缺陷可以通过强迫染色质松弛来部分挽救。综上所述，我们的研究结果表明，RNF 20/Bre 1 p介导的H2 B泛素化通过促进染色质松弛调节减数分裂重组，并建议一种旧的药物可能提供一种新的方法来治疗一些少精症或无精子症患者的染色质松弛障碍。
Meiotic recombination is essential for fertility in most sexually reproducing species, but the molecular mechanisms underlying this process remain poorly understood in mammals. Here, we show that RNF20-mediated H2B ubiquitination is required for meiotic recombination. A germ cell-specific knockout of the H2B ubiquitination E3 ligase RNF20 results in complete male infertility. The Stra8-Rnf20−/− spermatocytes arrest at the pachytene stage because of impaired programmed double-strand break (DSB) repair. Further investigations reveal that the depletion of RNF20 in the germ cells affects chromatin relaxation, thus preventing programmed DSB repair factors from being recruited to proper positions on the chromatin. The gametogenetic defects of the H2B ubiquitination deficient cells could be partially rescued by forced chromatin relaxation. Taken together, our results demonstrate that RNF20/Bre1p-mediated H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation, and suggest an old drug may provide a new way to treat some oligo- or azoospermia patients with chromatin relaxation disorders.
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