HDAC3 promotes meiotic apparatus assembly in mouse oocytes by modulating tubulin acetylation [RESEARCH ARTICLE]

Xiaoyan Li, Xiaohui Liu, Min Gao, Longsen Han, Danhong Qiu, Haichao Wang, Bo Xiong, Shao-Chen Sun, Honglin Liu, and Ling Gu

Histone deacetylases (HDACs) have been shown to deacetylate numerous cellular substrates that govern a wide array of biological processes. HDAC3, a member of the Class I HDACs, is a highly conserved and ubiquitously expressed protein. However, its roles in meiotic oocytes are not known. In the present study, we find that mouse oocytes depleted of HDAC3 are unable to completely progress through meiosis, and are blocked at metaphase I. These HDAC3 knockdown oocytes show spindle/chromosome organization failure, with severely impaired kinetochore-microtubule attachments. Consistent with this, the level of BubR1, a central component of the spindle assembly checkpoint, at kinetochores is dramatically increased in metaphase oocytes following HDAC3 depletion. Knockdown and overexpression experiments reveal that HDAC3 modulates the acetylation status of α-tubulin in mouse oocytes. Importantly, the deacetylation mimetic mutant tubulin-K40R can partly rescue the defective phenotypes of HDAC3 knockdown oocytes. Our data support a model whereby HDAC3, through deacetylating tubulin, promotes microtubule stability and the establishment of kinetochore-microtubule interaction, consequently ensuring proper spindle morphology, accurate chromosome movement and orderly meiotic progression during oocyte maturation.

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