The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair
Year: 2020
Type: article
Abstract: 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.
Source: eLife
DOI: 10.7554/elife.53459
Institutions: Shandong University, Chinese Academy of Sciences, Beijing Institute of Genomics, University of Chinese Academy of Sciences, Institute of Zoology, State Key Laboratory of Stem Cell and Reproductive Biology, Chinese University of Hong Kong, Center for Excellence in Molecular Cell Science
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: G243160991, G7259780143
OpenAlex ID: W3021014705