Dual histone methyl reader ZCWPW1 facilitates repair of meiotic double strand breaks in male mice
- The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, NIH, United States
- National Cancer Institute, NIH, United States
- University of Texas MD Anderson Cancer Center, United States
Abstract
Meiotic crossovers result from homology-directed repair of DNA double-strand breaks (DSBs). Unlike yeast and plants, where DSBs are generated near gene promoters, in many vertebrates DSBs are enriched at hotspots determined by the DNA binding activity of the rapidly evolving zinc finger array of PRDM9 (PR domain zinc finger protein 9). PRDM9 subsequently catalyzes tri-methylation of lysine 4 and lysine 36 of Histone H3 in nearby nucleosomes. Here, we identify the dual histone methylation reader ZCWPW1, which is tightly co-expressed during spermatogenesis with Prdm9, as an essential meiotic recombination factor required for efficient repair of PRDM9-dependent DSBs and for pairing of homologous chromosomes in male mice. In sum, our results indicate that the evolution of a dual histone methylation writer/reader (PRDM9/ZCWPW1) system in vertebrates remodeled genetic recombination hotspot selection from an ancestral static pattern near genes towards a flexible pattern controlled by the rapidly evolving DNA binding activity of PRDM9.
Data availability
All data have been deposited to GEO with the accession number GSE139289.
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Dual Histone Methyl Reader ZCWPW1 Facilitates Repair of Meiotic Double Strand BreaksNCBI Gene Expression Omnibus, GSE139289.
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Article and author information
Author details
Funding
National Institutes of Health (1ZIAHD008933)
- Todd S Macfarlan
National Institutes of Health (GM114306)
- Xiaodong Cheng
National Institutes of Health (CPRIT RR160029)
- Xiaodong Cheng
National Institutes of Health (Intramural Research Program)
- André Nussenzweig
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All mice experiments were done in accordance with NIH approved animal study protocol (ASP18-026).
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Dual histone methyl reader ZCWPW1 facilitates repair of meiotic double strand breaks in male mice
eLife 9:e53360.
https://doi.org/10.7554/eLife.53360
