Lu Yajuan, Dai Xiaoxin, Zhang Mianqun, Miao Yilong, Zhou Changyin, Cui Zhaokang, Xiong Bo
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Nucleic Acids Res. 2017 Sep 19;45(16):9388-9397. doi: 10.1093/nar/gkx563.
Sister chromatid cohesion, mediated by cohesin complex and established by the acetyltransferases Esco1 and Esco2, is essential for faithful chromosome segregation. Mutations in Esco2 cause Roberts syndrome, a developmental disease characterized by severe prenatal retardation as well as limb and facial abnormalities. However, its exact roles during oocyte meiosis have not clearly defined. Here, we report that Esco2 localizes to the chromosomes during oocyte meiotic maturation. Depletion of Esco2 by morpholino microinjection leads to the precocious polar body extrusion, the escape of metaphase I arrest induced by nocodazole treatment and the loss of BubR1 from kinetochores, indicative of inactivated SAC. Furthermore, depletion of Esco2 causes a severely impaired spindle assembly and chromosome alignment, accompanied by the remarkably elevated incidence of defective kinetochore-microtubule attachments which consequently lead to the generation of aneuploid eggs. Notably, we find that the involvement of Esco2 in SAC and kinetochore functions is mediated by its binding to histone H4 and acetylation of H4K16 both in vivo and in vitro. Thus, our data assign a novel meiotic function to Esco2 beyond its role in the cohesion establishment during mouse oocyte meiosis.
由黏连蛋白复合体介导并由乙酰转移酶Esco1和Esco2建立的姐妹染色单体黏连，对于准确的染色体分离至关重要。Esco2的突变会导致罗伯茨综合征，这是一种发育性疾病，其特征为严重的产前发育迟缓以及肢体和面部异常。然而，其在卵母细胞减数分裂过程中的具体作用尚未明确界定。在此，我们报告Esco2在卵母细胞减数分裂成熟过程中定位于染色体上。通过吗啉代显微注射耗尽Esco2会导致极体过早排出、诺考达唑处理诱导的中期I阻滞逃逸以及动粒上BubR1的丢失，这表明纺锤体组装检查点（SAC）失活。此外，耗尽Esco2会导致纺锤体组装和染色体排列严重受损，同时伴随着动粒 - 微管附着缺陷的发生率显著升高，从而导致非整倍体卵子的产生。值得注意的是，我们发现在体内和体外，Esco2参与SAC和动粒功能是通过其与组蛋白H4的结合以及H4K16的乙酰化介导的。因此，我们的数据赋予了Esco2在小鼠卵母细胞减数分裂过程中除了其在黏连建立中的作用之外的一种新的减数分裂功能。
