Institute of Physiological Chemistry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Department of Genes and Behaviour, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Life Sci Alliance. 2020 Feb 12;3(3). doi: 10.26508/lsa.201900564. Print 2020 Mar.
In mitotic cells, establishment of sister chromatid cohesion requires acetylation of the cohesin subunit SMC3 (acSMC3) by ESCO1 and/or ESCO2. Meiotic cohesin plays additional but poorly understood roles in the formation of chromosome axial elements (AEs) and synaptonemal complexes. Here, we show that levels of ESCO2, acSMC3, and the pro-cohesion factor sororin increase on meiotic chromosomes as homologs synapse. These proteins are less abundant on the largely unsynapsed sex chromosomes, whose sister chromatid cohesion appears weaker throughout the meiotic prophase. Using three distinct conditional knockout mouse strains, we demonstrate that ESCO2 is essential for male gametogenesis. Partial depletion of ESCO2 in prophase I spermatocytes delays chromosome synapsis and further weakens cohesion along sex chromosomes, which show extensive separation of AEs into single chromatids. Unsynapsed regions of autosomes are associated with the sex chromatin and also display split AEs. This study provides the first evidence for a specific role of ESCO2 in mammalian meiosis, identifies a particular ESCO2 dependence of sex chromosome cohesion and suggests support of autosomal synapsis by acSMC3-stabilized cohesion.
在有丝分裂细胞中，姐妹染色单体的黏合需要 ESCO1 和/或 ESCO2 将黏合蛋白亚基 SMC3 乙酰化（acSMC3）。 减数分裂黏合在染色体轴元件（AEs）和联会复合体的形成中发挥额外但了解甚少的作用。 在这里，我们表明，当同源物联会时，ESCO2、acSMC3 和前黏合因子 sororin 的水平会在减数分裂染色体上增加。 这些蛋白质在很大程度上未联会的性染色体上的丰度较低，其姐妹染色单体的黏合在整个减数分裂前期似乎较弱。 使用三种不同的条件性敲除小鼠品系，我们证明 ESCO2 对于雄性配子发生是必不可少的。 前期 I 精母细胞中 ESCO2 的部分耗竭会延迟染色体联会，并进一步削弱性染色体上的黏合，这导致 AE 广泛分离成单个染色单体。 常染色体的未联会区域与性染色质相关联，并且也显示出分离的 AE。 这项研究首次提供了 ESCO2 在哺乳动物减数分裂中特定作用的证据，确定了性染色体黏合的特定 ESCO2 依赖性，并表明 acSMC3 稳定的黏合支持常染色体联会。
