Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China
Shenli Yuan
CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
Lei Gao
CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
Mengjing Li
Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China
Xiaochen Yu
Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China
Jianhong Zhan
CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
Yingying Yin
Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China
Chao Liu
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
Chuanxin Zhang
Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China
Gang Lu
CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
Jiang Liu
CAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China; CAS Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China
Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
Hongbin Liu
Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China
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.
