Abstract
The histone modification writer Prdm9 has been shown to deposit H3K4me3 and H3K36me3 at future double-strand break (DSB) sites during the very early stages of meiosis, but the reader of these marks remains unclear. Here, we demonstrate that Zcwpw1 is an H3K4me3 reader that is required for DSB repair and synapsis in mouse testes. We generated H3K4me3 reader-dead Zcwpw1 mutant mice and found that their spermatocytes were arrested at the pachytene-like stage, which phenocopies the Zcwpw1 knock–out mice. Based on various ChIP-seq and immunofluorescence analyses using several mutants, we found that Zcwpw1's occupancy on chromatin is strongly promoted by the histone-modification activity of PRDM9. Zcwpw1 localizes to DMC1-labelled hotspots in a largely Prdm9-dependent manner, where it facilitates completion of synapsis by mediating the DSB repair process. In sum, our study demonstrates the function of ZCWPW1 that acts as part of the selection system for epigenetics-based recombination hotspots in mammals.
Data availability
The raw sequencing data produced in this study (ChIP-seq data listed in Supplemental Table S1) and RNA-seq data have been deposited to the Genome Sequence Archive (https://bigd.big.ac.cn/gsa/s/CjjpbIjf) under accession number PRJCA001901.
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The histone modification reader ZCWPW1 links histone methylation to repair of PRDM9-induced meiotic double stand breaksGenome Sequence Archive, PRJCA001901.
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In vivo binding of PRDM9 reveals interactions with noncanonical genomic sitesNCBI Gene Expression Omnibus, GSE93955.
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Cell-type-specific genomics reveals histone modification dynamics in mammalian meiosisNCBI Gene Expression Omnibus, GSE121760.
Article and author information
Author details
Funding
National Key Research and Development Programs of China (2018YFC1003400)
- Hongbin Liu
National Natural Science Foundation of China (31890780)
- Hongbin Liu
Shandong University (2016WLJH50)
- Hongbin Liu
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 were housed under controlled environmental conditions with free access to water and food, and illumination was on between 6 am and 6 pm. All experimental protocols were approved by the Animal Ethics Committee of the School of Medicine of Shandong University.
Reviewing Editor
- Bernard de Massy, CNRS UM, France
Publication history
- Received: November 8, 2019
- Accepted: May 5, 2020
- Accepted Manuscript published: May 6, 2020 (version 1)
- Version of Record published: June 24, 2020 (version 2)
- Version of Record updated: November 11, 2020 (version 3)
Copyright
© 2020, Huang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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