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Mol Cell. 2017 Sep 7;67(5):853-866.e5. doi: 10.1016/j.molcel.2017.07.011. Epub 2017 Aug 10.

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

Author information

1
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.
2
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.
3
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.
4
Jingjie PTM BioLab (Hangzhou), Co. Ltd., Hangzhou 310018, China.
5
School of Life Sciences, Tsinghua University, Beijing 100084, China.
6
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
7
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.
8
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; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. Electronic address: yshang@hsc.pku.edu.cn.

Abstract

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.

KEYWORDS:

CDYL; crotonyl-CoA hydratase; gene transcription; histone crotonylation; histone replacement; spermatogenesis

PMID:
28803779
DOI:
10.1016/j.molcel.2017.07.011
[Indexed for MEDLINE]
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