HELLS and PRDM9 form a pioneer complex to open chromatin at meiotic recombination hot spots
- Catrina Spruce,
- Sibongakonke Dlamini,
- Guruprasad Ananda,
- Naomi Bronkema,
- Hui Tian,
- Kenneth Paigen,
- Gregory W. Carter and
- Christopher L. Baker
- Corresponding author: christopher.baker{at}jax.org
Abstract
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.
Keywords
- H3K4me3
- chromatin remodeling
- germ cells
- histone modification
- meiosis
- nucleosome-depleted region
- pioneer factor
Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.333542.119.
- Received October 4, 2019.
- Accepted December 27, 2019.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
