Histone Acetyltransferase KAT8 is Essential for Mouse Oocyte Development by Regulating Reactive Oxygen Species Levels

Overview

Journal Development

Specialty Biology

Date 2017 May 17

PMID 28506985

Citations 20

Authors

Shi Yin

Xiaohua Jiang

Hanwei Jiang

Qian Gao

Fang Wang

Suixing Fan

Teka Khan

Nazish Jabeen

Manan Khan

Asim Ali

Peng Xu

Tej K Pandita

Heng-Yu Fan

Yuanwei Zhang

Qinghua Shi

Affiliations

Soon will be listed here.

Abstract

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 , regulates gene activity by acetylating histone H4 preferentially at lysine 16. To explore the function of KAT8 during mouse oocyte development, we crossed mice with mice to specifically delete in oocytes. Oocyte deletion resulted in female infertility, with follicle development failure in the secondary and preantral follicle stages. RNA-seq analysis revealed that 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 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.

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