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Chromodomain Protein CDYL Acts as a Crotonyl-CoA Hydratase to Regulate Histone Crotonylation and Spermatogenesis.
Molecular Cell ( IF 14.5 ) Pub Date : 2017-08-10 , DOI: 10.1016/j.molcel.2017.07.011 Shumeng Liu 1 , Huajing Yu 2 , Yongqing Liu 2 , Xinhua Liu 3 , Yu Zhang 2 , Chen Bu 4 , Shuai Yuan 2 , Zhe Chen 2 , Guojia Xie 2 , Wanjin Li 2 , Bosen Xu 2 , Jianguo Yang 2 , Lin He 2 , Tong Jin 2 , Yundong Xiong 2 , Luyang Sun 2 , Xiaohui Liu 5 , Chunsheng Han 6 , Zhongyi Cheng 4 , Jing Liang 2 , Yongfeng Shang 7
Molecular Cell ( IF 14.5 ) Pub Date : 2017-08-10 , DOI: 10.1016/j.molcel.2017.07.011 Shumeng Liu 1 , Huajing Yu 2 , Yongqing Liu 2 , Xinhua Liu 3 , Yu Zhang 2 , Chen Bu 4 , Shuai Yuan 2 , Zhe Chen 2 , Guojia Xie 2 , Wanjin Li 2 , Bosen Xu 2 , Jianguo Yang 2 , Lin He 2 , Tong Jin 2 , Yundong Xiong 2 , Luyang Sun 2 , Xiaohui Liu 5 , Chunsheng Han 6 , Zhongyi Cheng 4 , Jing Liang 2 , Yongfeng Shang 7
Affiliation
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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.
中文翻译：
染色体结构域蛋白CDYL充当巴豆酰辅酶A水合酶来调节组蛋白巴豆酰化和生精。
赖氨酸巴豆酰化（Kcr）是一种新近鉴定出的组蛋白修饰，与哺乳动物细胞中的活性转录有关。在这里我们报道，色域Y样转录共抑制子CDYL通过充当巴豆酰基-CoA水合酶将巴豆酰基-CoA转化为β-羟基丁酰基-CoA负调节组蛋白Kcr。我们显示，CDYL对组蛋白Kcr的负调控与它的转录抑制活性内在联系，并在圆形精子中性染色体连锁基因的激活和延长精子中的全基因组组蛋白替换中功能性地实现。值得注意的是，Cdyl转基因小鼠表现出组蛋白Kcr失调和雄性育性降低，附睾精子数量和精子细胞运动性降低。
更新日期：2017-08-10
中文翻译：
染色体结构域蛋白CDYL充当巴豆酰辅酶A水合酶来调节组蛋白巴豆酰化和生精。
赖氨酸巴豆酰化（Kcr）是一种新近鉴定出的组蛋白修饰，与哺乳动物细胞中的活性转录有关。在这里我们报道，色域Y样转录共抑制子CDYL通过充当巴豆酰基-CoA水合酶将巴豆酰基-CoA转化为β-羟基丁酰基-CoA负调节组蛋白Kcr。我们显示，CDYL对组蛋白Kcr的负调控与它的转录抑制活性内在联系，并在圆形精子中性染色体连锁基因的激活和延长精子中的全基因组组蛋白替换中功能性地实现。值得注意的是，Cdyl转基因小鼠表现出组蛋白Kcr失调和雄性育性降低，附睾精子数量和精子细胞运动性降低。
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