HELLS And PRDM9 form a pioneer complex to open chromatin at meiotic recombination hot spots.

Catrina Spruce, The Jackson Laboratory
Sibongakonke Dlamini
Guruprasad Ananda, The Jackson Laboratory
Naomi Bronkema
Hui Tian, The Jackson Laboratory
Kenneth Paigen, The Jackson Laboratory
Gregory W. Carter, The Jackson Laboratory
Christopher L. Baker, The Jackson Laboratory


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.