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

First Author  Spruce C Year  2020
Journal  Genes Dev PubMed ID  32001511
Mgi Jnum  J:283594 Mgi Id  MGI:6389086
Doi  10.1101/gad.333542.119 Citation  Spruce C, et al. (2020) HELLS And PRDM9 form a pioneer complex to open chromatin at meiotic recombination hot spots. Genes Dev 34:1-15
abstractText  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.
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