Dual function of Swc5 in SWR remodeling ATPase activation and histone H2A eviction.
Dual function of Swc5 in SWR remodeling ATPase activation and histone H2A eviction.
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DOI：
10.1093/nar/gkx589
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发表时间：
2017-09-29
影响因子：
14.9
通讯作者：
Luk E
中科院分区：
文献类型：
--
作者：
Sun L;Luk E
染色质重塑剂SWR通过ATP驱动的组蛋白交换反应将组蛋白H2A.Z沉积在启动子和其他调控位点，所述组蛋白交换反应用H2A.Z替换核小体H2 A。SWR与H2 A核小体和游离H2A.Z的同时结合诱导SWR ATP酶活性并参与组蛋白交换机制。Swc 5是14-多肽SWR复合物的保守亚基，其是组蛋白交换反应所需的，但其分子作用尚不清楚。我们发现，Swc 5，虽然不需要底物结合，是所需的SWR ATP酶的刺激，这表明，Swc 5需要耦合底物识别ATP酶激活。一个生化互补试验的开发，以显示一个独特的，保守的结构域在C-末端的Swc 5，称为Bucentaur（BCNT），是必不可少的组蛋白交换活性的SWR，而在N-末端的酸性区域是必需的最佳SWR功能。体外研究表明，Swc 5的酸性N-末端优先结合H2 A-H2 B二聚体，并表现出组蛋白伴侣活性。我们认为SWC 5在SWR中的辅助功能是当H2 A. Z插入核小体时协助H2 A排出。
The chromatin remodeler SWR deposits histone H2A.Z at promoters and other regulatory sites via an ATP-driven histone exchange reaction that replaces nucleosomal H2A with H2A.Z. Simultaneous binding of SWR to both H2A nucleosome and free H2A.Z induces SWR ATPase activity and engages the histone exchange mechanism. Swc5 is a conserved subunit of the 14-polypeptide SWR complex that is required for the histone exchange reaction, but its molecular role is unknown. We found that Swc5, although not required for substrate binding, is required for SWR ATPase stimulation, suggesting that Swc5 is required to couple substrate recognition to ATPase activation. A biochemical complementation assay was developed to show that a unique, conserved domain at the C-terminus of Swc5, called Bucentaur (BCNT), is essential for the histone exchange activity of SWR, whereas an acidic region at the N-terminus is required for optimal SWR function. In vitro studies showed the acidic N-terminus of Swc5 preferentially binds to the H2A–H2B dimer and exhibits histone chaperone activity. We propose that an auxiliary function of Swc5 in SWR is to assist H2A ejection as H2A.Z is inserted into the nucleosome.
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