HELLS and PRDM9 form a pioneer complex to open chromatin at meiotic recombination hot spots
HELLS and PRDM9 form a pioneer complex to open chromatin at meiotic recombination hot spots
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DOI：
10.1101/gad.333542.119
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发表时间：
2020-03-01
影响因子：
10.5
通讯作者：
Baker，Christopher L.
中科院分区：
文献类型：
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作者：
Spruce，Catrina;Dlamini，Sibongakonke;Baker，Christopher L.
染色质屏障防止调节元件和DNA结合蛋白之间的虚假相互作用。一个这样的障碍，其克服机制知之甚少，是在减数分裂过程中重组热点的访问。在这里，我们表明，染色质重塑HELLS和DNA结合蛋白PRDM9功能一起打开染色质的热点，并提供访问的DNA双链断裂（DSB）机制。修饰热点由在其他调控元件中未发现的组蛋白修饰的独特组合来修饰。HELLS被PRDM9招募到热点，并且对于组蛋白修饰和热点处的DNA可及性都是必需的。在缺乏HELLS的雄性小鼠中，DSB被重新定位到开放染色质的其他位点，导致生殖细胞死亡和不育。总之，这些数据提供了热点激活的模型，其中HELLS和PRDM9形成先锋复合物以创建开放染色质的独特表观基因组环境，从而允许DSB的正确放置和修复。
Chromatin barriers prevent spurious interactions between regulatory elements and DNA-binding proteins. One such barrier, whose mechanism for overcoming is poorly understood, is access to recombination hot spots during meiosis. Here we show that the chromatin remodeler HELLS and DNA-binding protein PRDM9 function together to open chromatin at hot spots and provide access for the DNA double-strand break (DSB) machinery. Recombination hot spots are decorated by a unique combination of histone modifications not found at other regulatory elements. HELLS is recruited to hot spots by PRDM9 and is necessary for both histone modifications and DNA accessibility at hot spots. In male mice lacking HELLS, DSBs are retargeted to other sites of open chromatin, leading to germ cell death and sterility. Together, these data provide a model for hot spot activation in which HELLS and PRDM9 form a pioneer complex to create a unique epigenomic environment of open chromatin, permitting correct placement and repair of DSBs.