Li Xiaoyan, Liu Xiaohui, Gao Min, Han Longsen, Qiu Danhong, Wang Haichao, Xiong Bo, Sun Shao-Chen, Liu Honglin, Gu Ling
College of Animal Science & Technology, Nanjing Agricultural University, 210095 Nanjing, China.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 211166 Nanjing, China.
Development. 2017 Oct 15;144(20):3789-3797. doi: 10.1242/dev.153353. Epub 2017 Sep 21.
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.
组蛋白去乙酰化酶（HDACs）已被证明能使众多调控广泛生物过程的细胞底物去乙酰化。HDAC3是I类HDACs的成员之一，是一种高度保守且广泛表达的蛋白质。然而，其在减数分裂卵母细胞中的作用尚不清楚。在本研究中，我们发现缺失HDAC3的小鼠卵母细胞无法完全完成减数分裂，阻滞在减数第一次分裂中期。这些HDAC3敲低的卵母细胞表现出纺锤体/染色体组织紊乱，着丝粒 - 微管附着严重受损。与此一致的是，在HDAC3缺失后的中期卵母细胞中，着丝粒处纺锤体组装检查点的核心成分BubR1水平显著增加。敲低和过表达实验表明，HDAC3调节小鼠卵母细胞中α - 微管蛋白的乙酰化状态。重要的是，去乙酰化模拟突变体微管蛋白 - K40R可以部分挽救HDAC3敲低卵母细胞的缺陷表型。我们的数据支持一种模型，即HDAC3通过使微管蛋白去乙酰化，促进微管稳定性和着丝粒 - 微管相互作用的建立，从而确保卵母细胞成熟过程中纺锤体形态正常、染色体准确移动和减数分裂有序进行。
