title: H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation.
abstract: Meiotic recombination is essential for fertility in most sexually reproducing species, but the molecular mechanisms underlying this process remain poorly understood in mammals. Here, we show that RNF20-mediated H2B ubiquitination is required for meiotic recombination. A germ cell-specific knockout of the H2B ubiquitination E3 ligase RNF20 results in complete male infertility. The Stra8-Rnf20-/-spermatocytes arrest at the pachytene stage because of impaired programmed double-strand break (DSB) repair. Further investigations reveal that the depletion of RNF20 in the germ cells affects chromatin relaxation, thus preventing programmed DSB repair factors from being recruited to proper positions on the chromatin. The gametogenetic defects of the H2B ubiquitination deficient cells could be partially rescued by forced chromatin relaxation. Taken together, our results demonstrate that RNF20/Bre1p-mediated H2B ubiquitination regulates meiotic recombination by promoting chromatin relaxation, and suggest an old drug may provide a new way to treat some oligo- or azoospermia patients with chromatin relaxation disorders.
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Song
authors.affiliation: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Li
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Huayu
authors.initials: H
authors.lastname: Tu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Weixiao
authors.initials: W
authors.lastname: Liu
authors.affiliation: College of Marine Life, Ocean University of China, Qingdao 266003, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yuanting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Shang
authors.affiliation: Reproductive Biology Group, Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands.
authors.forename: Dirk G
authors.initials: DG
authors.lastname: de Rooij
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China leways@ioz.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency; D000818:Animals; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D005260:Female; D005854:Germ Cells / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D007248:Infertility, Male / Q000235:genetics; D008297:Male; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D049471:Pachytene Stage / Q000235:genetics; D011995:Recombination, Genetic; D013090:Spermatocytes / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D006657:Histones; C102019:Stra8 protein, mouse; C571257:RNF20 protein, mouse; D044767:Ubiquitin-Protein Ligases