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.

中文翻译：

---

HELLS 和 PRDM9 形成先驱复合物，在减数分裂重组热点处打开染色质。

染色质屏障可防止调节元件和 DNA 结合蛋白之间的虚假相互作用。一种这样的障碍，其克服机制知之甚少，是在减数分裂过程中进入重组热点。在这里，我们表明染色质重塑因子 HELLS 和 DNA 结合蛋白 PRDM9 共同发挥作用，在热点处打开染色质，并为 DNA 双链断裂 (DSB) 机制提供通路。重组热点由组蛋白修饰的独特组合修饰，这些组蛋白修饰在其他调控元件中未发现。HELLS 被 PRDM9 招募到热点，并且对于热点处的组蛋白修饰和 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。一起，