CNRS UMR 6290, University of Rennes 1, IGDR (Institut de Génétique et Développement de Rennes), 35043 Rennes cedex, France.
Epigenetics and Cancer Laboratory, IGDR Rennes, France.
J Cell Sci. 2023 Jun 1;136(11). doi: 10.1242/jcs.261014. Epub 2023 Jun 8.
Sister chromatid cohesion is a multi-step process implemented throughout the cell cycle to ensure the correct transmission of chromosomes to daughter cells. Although cohesion establishment and mitotic cohesion dissolution have been extensively explored, the regulation of cohesin loading is still poorly understood. Here, we report that the methyltransferase NSD3 is essential for mitotic sister chromatid cohesion before mitosis entry. NSD3 interacts with the cohesin loader complex kollerin (composed of NIPBL and MAU2) and promotes the chromatin recruitment of MAU2 and cohesin at mitotic exit. We also show that NSD3 associates with chromatin in early anaphase, prior to the recruitment of MAU2 and RAD21, and dissociates from chromatin when prophase begins. Among the two NSD3 isoforms present in somatic cells, the long isoform is responsible for regulating kollerin and cohesin chromatin-loading, and its methyltransferase activity is required for efficient sister chromatid cohesion. Based on these observations, we propose that NSD3-dependent methylation contributes to sister chromatid cohesion by ensuring proper kollerin recruitment and thus cohesin loading.
姐妹染色单体黏合是一个贯穿细胞周期的多步过程，旨在确保染色体正确传递给子细胞。尽管黏合的建立和有丝分裂中的黏合解体已经得到了广泛的研究，但黏合蛋白加载的调控仍知之甚少。在这里，我们报告说，甲基转移酶 NSD3 在有丝分裂进入之前对于有丝分裂姐妹染色单体黏合是必不可少的。NSD3 与黏合蛋白加载复合物 kollerin（由 NIPBL 和 MAU2 组成）相互作用，并促进 MAU2 和黏合蛋白在有丝分裂后期向染色质的募集。我们还表明，NSD3 在前期开始之前，在招募 MAU2 和 RAD21 之前，与早期后期的染色质相关联，并在前期开始时从染色质上解离。在体细胞中存在的两种 NSD3 同种型中，长同种型负责调节 kollerin 和黏合蛋白染色质加载，并且其甲基转移酶活性对于有效的姐妹染色单体黏合是必需的。基于这些观察结果，我们提出 NSD3 依赖性甲基化通过确保适当的 kollerin 募集，从而确保黏合蛋白加载，有助于姐妹染色单体黏合。
