ISW1a modulates cohesin distribution in centromeric and pericentromeric regions.
ISW1a modulates cohesin distribution in centromeric and pericentromeric regions.
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DOI：
10.1093/nar/gkad612
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发表时间：
2023-09-22
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
--
作者：
凝聚素是一种高度保守的多蛋白复合物，其典型功能是将姐妹染色单体保持在一起以确保染色体精确分离。粘着蛋白与染色质的结合依赖于Scc 2-Scc 4粘着蛋白加载复合物，该复合物能够使粘着蛋白开环和姐妹DNA的拓扑截留。为了更好地了解姐妹染色单体的凝聚力是如何调节的，我们进行了蛋白质组学筛选在芽殖酵母，确定Isw 1染色质重塑作为一个结合伴侣。此外，我们发现Isw 1还与Scc 2-Scc 4相互作用。Isw 1蛋白、ISW 1a的Ioc 3亚基或Isw 1染色质重塑活性的缺乏导致了着丝粒和近着丝粒处粘附素的积累增加，这表明ISW 1a可能促进粘附素从装载的着丝粒位点有效地易位到邻近区域。与ISW 1a在着丝粒区域的染色质组织中的作用一致，Isw 1被发现被募集到着丝粒。在它的情况下，我们观察到在着丝粒和近着丝粒的核小体景观的变化。最后，我们发现当RSC功能丧失时，ISW 1a活性导致减少的粘着蛋白结合和内聚缺陷。两者合计，我们的研究结果支持的概念，在染色体上的粘着蛋白分布的调节中的染色质重塑的关键作用。
Cohesin is a highly conserved, multiprotein complex whose canonical function is to hold sister chromatids together to ensure accurate chromosome segregation. Cohesin association with chromatin relies on the Scc2-Scc4 cohesin loading complex that enables cohesin ring opening and topological entrapment of sister DNAs. To better understand how sister chromatid cohesion is regulated, we performed a proteomic screen in budding yeast that identified the Isw1 chromatin remodeler as a cohesin binding partner. In addition, we found that Isw1 also interacts with Scc2-Scc4. Lack of Isw1 protein, the Ioc3 subunit of ISW1a or Isw1 chromatin remodeling activity resulted in increased accumulation of cohesin at centromeres and pericentromeres, suggesting that ISW1a may promote efficient translocation of cohesin from the centromeric site of loading to neighboring regions. Consistent with the role of ISW1a in the chromatin organization of centromeric regions, Isw1 was found to be recruited to centromeres. In its absence we observed changes in the nucleosomal landscape at centromeres and pericentromeres. Finally, we discovered that upon loss of RSC functionality, ISW1a activity leads to reduced cohesin binding and cohesion defect. Taken together, our results support the notion of a key role of chromatin remodelers in the regulation of cohesin distribution on chromosomes.
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影响因子：
5.3
作者：
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影响因子：
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通讯作者：
Marston, Adele L.