The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair

The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair

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...

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Main Authors: Tao Huang, Shenli Yuan, Lei Gao, Mengjing Li, Xiaochen Yu, Jianhong Zhan, Yingying Yin, Chao Liu, Chuanxin Zhang, Gang Lu, Wei Li, Jiang Liu, Zi-Jiang Chen, Hongbin Liu
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-05-01
Series:eLife
Subjects:
meiosis
ZCWPW1
PRDM9
histone modification
DNA double-strand breaks
homologous recombination
Online Access:https://elifesciences.org/articles/53459
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record_format Article
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language English
format Article
sources DOAJ
author Tao Huang
Shenli Yuan
Lei Gao
Mengjing Li
Xiaochen Yu
Jianhong Zhan
Yingying Yin
Chao Liu
Chuanxin Zhang
Gang Lu
Wei Li
Jiang Liu
Zi-Jiang Chen
Hongbin Liu
spellingShingle Tao Huang
Shenli Yuan
Lei Gao
Mengjing Li
Xiaochen Yu
Jianhong Zhan
Yingying Yin
Chao Liu
Chuanxin Zhang
Gang Lu
Wei Li
Jiang Liu
Zi-Jiang Chen
Hongbin Liu
The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair
eLife
meiosis
ZCWPW1
PRDM9
histone modification
DNA double-strand breaks
homologous recombination
author_facet Tao Huang
Shenli Yuan
Lei Gao
Mengjing Li
Xiaochen Yu
Jianhong Zhan
Yingying Yin
Chao Liu
Chuanxin Zhang
Gang Lu
Wei Li
Jiang Liu
Zi-Jiang Chen
Hongbin Liu
author_sort Tao Huang
title The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair
title_short The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair
title_full The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair
title_fullStr The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair
title_full_unstemmed The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair
title_sort histone modification reader zcwpw1 links histone methylation to prdm9-induced double-strand break repair
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2020-05-01
description 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.
topic meiosis
ZCWPW1
PRDM9
histone modification
DNA double-strand breaks
homologous recombination
url https://elifesciences.org/articles/53459
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spelling doaj-e5347438168f41b892eb82ce181ef10c2021-05-05T21:04:42ZengeLife Sciences Publications LtdeLife2050-084X2020-05-01910.7554/eLife.53459The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repairTao Huang0https://orcid.org/0000-0002-7086-570XShenli Yuan1Lei Gao2Mengjing Li3Xiaochen Yu4Jianhong Zhan5Yingying Yin6Chao Liu7Chuanxin Zhang8Gang Lu9Wei Li10https://orcid.org/0000-0002-6235-0749Jiang Liu11Zi-Jiang Chen12https://orcid.org/0000-0001-6637-6631Hongbin Liu13Center 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, ChinaCAS 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, ChinaCAS Key Laboratory of Genome Sciences and Information, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, ChinaCenter 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, ChinaCenter 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, ChinaCAS 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, ChinaCenter 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, ChinaState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaCenter 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, ChinaCUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, ChinaState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, ChinaCAS 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, ChinaCenter 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, ChinaCenter 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, ChinaThe 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.https://elifesciences.org/articles/53459meiosisZCWPW1PRDM9histone modificationDNA double-strand breakshomologous recombination

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