College of Animal Science and Technology, Nanjing Agricultural University , Nanjing , China.
Cell Cycle. 2019 Oct;18(19):2481-2494. doi: 10.1080/15384101.2019.1651162. Epub 2019 Aug 6.
In mammalian cells, cohesin acetyltransferases Esco1 and Esco2 acetylate cohesin subunit Smc3 to establish chromosome cohesion, ensuring the accurate chromosome segregation. However, we have previously documented that both Esco1 and Esco2 have unique substrates and roles in mouse oocyte meiosis I to orchestrate the meiotic progression, but whether these functions are conserved among species is still not determined. Here, we used porcine oocytes as a model to illustrate that Esco1 and Esco2 exerted conserved functions during oocyte meiosis. We observed that Esco1 and Esco2 exhibited different localization patterns in porcine oocytes. Esco1 was localized to the spindle apparatus while Esco2 was distributed on the chromosomes. Depletion of Esco1 by siRNA microinjection caused the meiotic arrest by showing the reduced frequency of first polar body extrusion and defective spindle/chromosome structure. In addition, Esco1 bound to α-tubulin and was required for its acetylation level to maintain the microtubule dynamics. By contrast, depletion of Esco2 by siRNA microinjection resulted in the accelerated meiotic progression by displaying the precocious polar body extrusion and inactivation of spindle assembly checkpoint. Notably, Esco2 was shown to be associated with histone H4 for the acetylation of H4K16 to modulate the kinetochore function. Collectively, our data reveal that Esco1 and Esco2 perform distinct and conserved functions in oocytes to drive the meiotic progression beyond their canonical roles in the cohesion establishment.
在哺乳动物细胞中,黏连蛋白乙酰转移酶 Esco1 和 Esco2 乙酰化黏连蛋白亚基 Smc3,以建立染色体黏连,确保染色体的准确分离。然而,我们之前已经记录到,Esco1 和 Esco2 在小鼠卵母细胞减数分裂 I 中具有独特的底物和作用,以协调减数分裂进程,但这些功能是否在物种间保守尚未确定。在这里,我们使用猪卵母细胞作为模型来阐明 Esco1 和 Esco2 在卵母细胞减数分裂中发挥保守功能。我们观察到 Esco1 和 Esco2 在猪卵母细胞中表现出不同的定位模式。Esco1 定位在纺锤体装置上,而 Esco2 分布在染色体上。通过 siRNA 微注射耗尽 Esco1 导致减数分裂停滞,表现为第一极体排出频率降低和纺锤体/染色体结构缺陷。此外,Esco1 与α-微管蛋白结合,并需要其乙酰化水平来维持微管动力学。相比之下,通过 siRNA 微注射耗尽 Esco2 导致减数分裂进程加速,表现为极体过早排出和纺锤体组装检查点失活。值得注意的是,Esco2 与组蛋白 H4 相关,用于乙酰化 H4K16 以调节动粒功能。总之,我们的数据表明,Esco1 和 Esco2 在卵母细胞中发挥独特和保守的功能,以推动减数分裂进程超越其在黏合建立中的经典作用。