RT Journal Article
SR Electronic
T1 The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double strand break repair
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 836023
DO 10.1101/836023
A1 Tao Huang
A1 Shenli Yuan
A1 Lei Gao
A1 Mengjing Li
A1 Xiaochen Yu
A1 Jianhong Zhang
A1 Yingying Yin
A1 Chao Liu
A1 Chuanxin Zhang
A1 Gang Lu
A1 Wei Li
A1 Jiang Liu
A1 Zi-Jiang Chen
A1 Hongbin Liu
YR 2020
UL http://biorxiv.org/content/early/2020/05/05/836023.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.