Histone acetyltransferase KAT8 is essential for mouse oocyte development by regulating reactive oxygen species levels

被引:47
|
作者
Yin, Shi [1 ]
Jiang, Xiaohua [1 ]
Jiang, Hanwei [1 ]
Gao, Qian [1 ]
Wang, Fang [1 ]
Fan, Suixing [1 ]
Khan, Teka [1 ]
Jabeen, Nazish [1 ]
Khan, Manan [1 ]
Ali, Asim [1 ]
Xu, Peng [2 ]
Pandita, Tej K. [3 ]
Fan, Heng-Yu [4 ]
Zhang, Yuanwei [1 ]
Shi, Qinghua [1 ]
机构
[1] Univ Sci & Technol China, Collaborat Innovat Ctr Genet & Dev,Mol & Cell Gen, Collaborat Innovat Ctr Canc Med,CAS Key Lab Innat, CAS Ctr Excellence Mol Cell Sci,Sch Life Sci,Hefe, Hefei 230027, Anhui, Peoples R China
[2] USTC Shenyang Jinghua Hosp Joint Ctr Human Reprod, Shenyang 110000, Liaoning, Peoples R China
[3] Houston Methodist Res Inst, Dept Radiat Oncol, Houston, TX 75390 USA
[4] Zhejiang Univ, Life Sci Inst, Hangzhou 310058, Zhejiang, Peoples R China
来源
DEVELOPMENT | 2017年 / 144卷 / 12期
基金
中国国家自然科学基金; 美国国家卫生研究院;
关键词
Kat8; H4K16ac; Oocyte; Follicle; Sterility; ROS; STRAND BREAK REPAIR; N-ACETYLCYSTEINE; OXIDATIVE STRESS; H4; ACETYLATION; MAMMALIAN OOCYTES; LYSINE; 16; MICE; MOF; CELLS; DAMAGE;
D O I
10.1242/dev.149518
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Proper oocyte development is crucial for female fertility and requires timely and accurate control of gene expression. K (lysine) acetyltransferase 8 (KAT8), an important component of the X chromosome dosage compensation system in Drosophila, regulates gene activity by acetylating histone H4 preferentially at lysine 16. To explore the function of KAT8 during mouse oocyte development, we crossed Kat8(flox/flox) mice with Gdf9-Cre mice to specifically delete Kat8 in oocytes. Oocyte Kat8 deletion resulted in female infertility, with follicle development failure in the secondary and preantral follicle stages. RNA-seq analysis revealed that Kat8 deficiency in oocytes results in significant downregulation of antioxidant genes, with a consequent increase in reactive oxygen species. Intraperitoneal injection of the antioxidant N-acetylcysteine rescued defective follicle and oocyte development resulting from Kat8 deficiency. Chromatin immunoprecipitation assays indicated that KAT8 regulates antioxidant gene expression by direct binding to promoter regions. Taken together, our findings demonstrate that KAT8 is essential for female fertility by regulating antioxidant gene expression and identify KAT8 as the first histone acetyltransferase with an essential function in oogenesis.
引用
收藏
页码:2165 / 2174
页数:10
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