• PMID: 28803779
• Gene Name: CDYL
• Condition: Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

Chromodomain Protein CDYL Acts as a Crotonyl-CoA Hydratase to Regulate Histone Crotonylation and Spermatogenesis

Liu S, Yu H, Liu Y, Liu X, Zhang Y, Bu C, Yuan S, Chen Z, Xie G, Li W, Xu B, Yang J, He L, Jin T, Xiong Y, Sun L, Liu X, Han C, Cheng Z, Liang J, Shang Y.

Lysine crotonylation (Kcr) is a newly identified histone modification that is associated with active transcription in mammalian cells. Here we report that the chromodomain Y-like transcription corepressor CDYL negatively regulates histone Kcr by acting as a crotonyl-CoA hydratase to convert crotonyl-CoA to β-hydroxybutyryl-CoA. We showed that the negative regulation of histone Kcr by CDYL is intrinsically linked to its transcription repression activity and functionally implemented in the reactivation of sex chromosome-linked genes in round spermatids and genome-wide histone replacement in elongating spermatids. Significantly, Cdyl transgenic mice manifest dysregulation of histone Kcr and reduction of male fertility with a decreased epididymal sperm count and sperm cell motility. Our study uncovers a biochemical pathway in the regulation of histone Kcr and implicates CDYL-regulated histone Kcr in spermatogenesis, adding to the understanding of the physiology of male reproduction and the mechanism of the spermatogenic failure in AZFc (Azoospermia Factor c)-deleted infertile men. CI - Copyright © 2017 Elsevier Inc. All rights reserved. FAU - Liu, Shumeng AU - Liu S AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. FAU - Yu, Huajing AU - Yu H AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - Liu, Yongqing AU - Liu Y AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - Liu, Xinhua AU - Liu X AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. FAU - Zhang, Yu AU - Zhang Y AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - Bu, Chen AU - Bu C AD - Jingjie PTM BioLab (Hangzhou), Co. Ltd., Hangzhou 310018, China. FAU - Yuan, Shuai AU - Yuan S AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - Chen, Zhe AU - Chen Z AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - Xie, Guojia AU - Xie G AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - Li, Wanjin AU - Li W AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - Xu, Bosen AU - Xu B AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - Yang, Jianguo AU - Yang J AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - He, Lin AU - He L AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - Jin, Tong AU - Jin T AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - Xiong, Yundong AU - Xiong Y AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - Sun, Luyang AU - Sun L AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. FAU - Liu, Xiaohui AU - Liu X AD - School of Life Sciences, Tsinghua University, Beijing 100084, China. FAU - Han, Chunsheng AU - Han C AD - State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. FAU - Cheng, Zhongyi AU - Cheng Z AD - Jingjie PTM BioLab (Hangzhou), Co. Ltd., Hangzhou 310018, China. FAU - Liang, Jing AU - Liang J AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: liang_jing@hsc.pku.edu.cn.