PT  - JOURNAL ARTICLE
AU  - Spruce, Catrina
AU  - Dlamini, Sibongakonke
AU  - Ananda, Guruprasad
AU  - Bronkema, Naomi
AU  - Tian, Hui
AU  - Paigen, Ken
AU  - Carter, Gregory W.
AU  - Baker, Christopher L
TI  - HELLS and PRDM9 form a Pioneer Complex to Open Chromatin at Meiotic Recombination Hotspots
AID  - 10.1101/764183
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 764183
4099  - http://biorxiv.org/content/early/2019/09/10/764183.short
4100  - http://biorxiv.org/content/early/2019/09/10/764183.full
AB  - 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 hotspots during meiosis. Here we show that the chromatin remodeler HELLS and DNA-binding protein PRDM9 function together to open chromatin at hotspots and provide access for the DNA double-strand break (DSB) machinery. Recombination hotspots are decorated by a unique combination of histone modifications, not found at other regulatory elements. HELLS is recruited to hotspots by PRDM9, and is necessary for both histone modifications and DNA accessibility at hotspots. 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 hotspot activation where HELLS and PRDM9 function as a pioneer complex to create a unique epigenomic environment of open chromatin, permitting correct placement and repair of DSBs.