• PMID: 31189663
• Gene Name: PHF7
• Condition: Male infertility
• Association: Associated
• Mutation: Deletion of PHF7
• Sex: Male
• Infertility type: Male infertility

PHF7 is a novel histone H2A E3 ligase prior to histone-to-protamine exchange during spermiogenesis

Wang X, Kang JY, Wei L, Yang X, Sun H, Yang S, Lu L, Yan M, Bai M, Chen Y, Long J, Li N, Li D, Huang J, Lei M, Shao Z, Yuan W, Zuo E, Lu K, Liu MF, Li J.

Epigenetic regulation, including histone-to-protamine exchanges, controls spermiogenesis. However, the underlying mechanisms of this regulation are largely unknown. Here, we report that PHF7, a testis-specific PHD and RING finger domain-containing protein, is essential for histone-to-protamine exchange in mice. PHF7 is specifically expressed during spermiogenesis. PHF7 deletion results in male infertility due to aberrant histone retention and impaired protamine replacement in elongated spermatids. Mechanistically, PHF7 can simultaneously bind histone H2A and H3; its PHD domain, a histone code reader, can specifically bind H3K4me3/me2, and its RING domain, a histone writer, can ubiquitylate H2A. Thus, our study reveals that PHF7 is a novel E3 ligase that can specifically ubiquitylate H2A through binding H3K4me3/me2 prior to histone-to-protamine exchange. CI - © 2019. Published by The Company of Biologists Ltd. FAU - Wang, Xiukun AU - Wang X AD - State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Science, University of Chinese Academy of Science, Shanghai 200031, China. FAU - Kang, Jun-Yan AU - Kang JY AD - State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Science, University of Chinese Academy of Science, Shanghai 200031, China. FAU - Wei, Leixin AU - Wei L AD - State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Science, University of Chinese Academy of Science, Shanghai 200031, China. AD - Department of Orthopaedic Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China. FAU - Yang, Xiaogan AU - Yang X AD - State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, Guangxi 530004, China. FAU - Sun, Hongduo AU - Sun H AD - Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. FAU - Yang, Suming AU - Yang S AD - State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Science, University of Chinese Academy of Science, Shanghai 200031, China. FAU - Lu, Lei AU - Lu L AD - State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Science, University of Chinese Academy of Science, Shanghai 200031, China. FAU - Yan, Meng AU - Yan M AD - State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Science, University of Chinese Academy of Science, Shanghai 200031, China. FAU - Bai, Meizhu AU - Bai M AD - State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Science, University of Chinese Academy of Science, Shanghai 200031, China. FAU - Chen, Yanyan AU - Chen Y AD - National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 333 Haike Road, Shanghai 201203, China. FAU - Long, Juanjuan AU - Long J AD - National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 333 Haike Road, Shanghai 201203, China. FAU - Li, Na AU - Li N AD - State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Science, University of Chinese Academy of Science, Shanghai 200031, China. FAU - Li, Dangsheng AU - Li D AD - CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Science, Shanghai 200031, China. FAU - Huang, Jing AU - Huang J AD - National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 333 Haike Road, Shanghai 201203, China. FAU - Lei, Ming AU - Lei M AD - National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 333 Haike Road, Shanghai 201203, China. FAU - Shao, Zhen AU - Shao Z AD - Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. FAU - Yuan, Wen AU - Yuan W AUID- ORCID: 0000-0002-6394-344X AD - Department of Orthopaedic Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China jsli@sibcb.ac.cn mfliu@sibcb.ac.cn kehuanlu@163.com erweizuo@163.com yuanwenspine@163.com. FAU - Zuo, Erwei AU - Zuo E AUID- ORCID: 0000-0002-7094-0933 AD - State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, Guangxi 530004, China jsli@sibcb.ac.cn mfliu@sibcb.ac.cn kehuanlu@163.com erweizuo@163.com yuanwenspine@163.com. AD - Research Center of Animal Genomics, Agricultural Genomics Institute at Shengzhen, Chinese Academy of Agricultural Sciences, Shengzhen, Guangdong 518210, China. FAU - Lu, Kehuan AU - Lu K AUID- ORCID: 0000-0002-9443-1236 AD - State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Animal Reproduction Institute, Guangxi University, Nanning, Guangxi 530004, China jsli@sibcb.ac.cn mfliu@sibcb.ac.cn kehuanlu@163.com erweizuo@163.com yuanwenspine@163.com. FAU - Liu, Mo-Fang AU - Liu MF AUID- ORCID: 0000-0003-1800-466X AD - State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Science, University of Chinese Academy of Science, Shanghai 200031, China jsli@sibcb.ac.cn mfliu@sibcb.ac.cn kehuanlu@163.com erweizuo@163.com yuanwenspine@163.com.