Genes and Behavior Department, Max Planck Institute for Biophysical Chemistry, Goettingen, Germany.
EMBO J. 2012 Jan 4;31(1):71-82. doi: 10.1038/emboj.2011.381. Epub 2011 Nov 18.
Sister chromatid cohesion, mediated by cohesin and regulated by Sororin, is essential for chromosome segregation. In mammalian cells, cohesion establishment and Sororin recruitment to chromatin-bound cohesin depends on the acetyltransferases Esco1 and Esco2. Mutations in Esco2 cause Roberts syndrome, a developmental disease in which mitotic chromosomes have a 'railroad' track morphology. Here, we show that Esco2 deficiency leads to termination of mouse development at pre- and post-implantation stages, indicating that Esco2 functions non-redundantly with Esco1. Esco2 is transiently expressed during S-phase when it localizes to pericentric heterochromatin (PCH). In interphase, Esco2 depletion leads to a reduction in cohesin acetylation and Sororin recruitment to chromatin. In early mitosis, Esco2 deficiency causes changes in the chromosomal localization of cohesin and its protector Sgo1. Our results suggest that Esco2 is needed for cohesin acetylation in PCH and that this modification is required for the proper distribution of cohesin on mitotic chromosomes and for centromeric cohesion.
姐妹染色单体黏合，由黏合蛋白介导并受 Sororin 调控，对于染色体分离至关重要。在哺乳动物细胞中，黏合的建立和 Sororin 募集到染色质结合的黏合蛋白依赖于乙酰转移酶 Esco1 和 Esco2。Esco2 突变会导致 Roberts 综合征，这是一种发育疾病，其中有丝分裂染色体呈现“铁轨”样形态。在这里，我们表明 Esco2 缺乏会导致小鼠在植入前和植入后阶段的发育终止，表明 Esco2 与 Esco1 非冗余地发挥作用。Esco2 在 S 期表达，此时它定位于着丝粒异染色质（PCH）。在间期中，Esco2 耗竭会导致黏合蛋白乙酰化减少和 Sororin 募集到染色质。在早期有丝分裂中，Esco2 缺乏会导致黏合蛋白及其保护蛋白 Sgo1 在染色体上的定位发生变化。我们的结果表明，Esco2 对于 PCH 中黏合蛋白的乙酰化是必需的，这种修饰对于黏合蛋白在有丝分裂染色体上的正确分布以及着丝粒黏合是必需的。
