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Functional Roles of Acetylated Histone Marks at Mouse Meiotic Recombination Hotspots (sequencing)

ABSTRACT: Meiotic recombination is initiated by the Spo11 endonuclease, which directs DNA DSBs. We report here that the recombinogenic cores of active hotspots in mice harbor several histone H3 and H4 acetylation and methylation marks that are typical of open, active chromatin. Further, deposition of these histone marks is dynamic and manifest at spermatogonia and/or pre-leptotene meiotic cells, which would facilitate the formation of DSBs at leptotene. Importantly, there was concordance in the overlap of the histone mark ChIP profiles with nucleosome occupancy maps, which were determined by real-time PCR and whole genome sequencing (WGS) analyses of micococcal-nuclease resistance regions across four mouse meiotic hotspots (HS22, HS59.4, HS59.5 and HS61.1). Our study reveals that there are instructive roles of histone acetylated marks at meiotic recombination hotspot cores and that they are necessary to promote hotspot activity and crossover resolution.

ORGANISM(S): Mus musculus

PROVIDER: GSE87057 | GEO | 2016/11/04

SECONDARY ACCESSION(S): PRJNA343463

REPOSITORIES: GEO

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Functional roles of Acetylated Histone Marks at Mouse Meiotic Recombination Hotspots (expression)

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Histone H3 lysine9 acetylation, rather than lysine4 trimethylation, marks meiotic recombination hotspots and promotes recombination initiation in fission yeast

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Histone H3 lysine9 acetylation, rather than lysine4 trimethylation, marks meiotic recombination hotspots and promotes recombination initiation in fission yeast

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Genome-wide map of H3K4me3 and PRDM9-binding in 12 day post-partum mouse spermatocytes

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HELLS and PRDM9 from a pioneer complex to open chromatin at meiotic recombination hotspots

Project description: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 identify that the DNA-binding protein PRDM9 and chromatin remodeler HELLS function together to open chromatin at hotspots providing access to 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 by PRDM9, and is necessary for both histone modification 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 to open chromatin in preparation for proper placement and repair of DSBs.

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