Wu Wei-Hua, Alami Samar, Luk Edward, Wu Chwen-Huey, Sen Subhojit, Mizuguchi Gaku, Wei Debbie, Wu Carl
Laboratory of Molecular Cell Biology, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Building 37, Room 6068, Bethesda, Maryland 20892-4255, USA.
Nat Struct Mol Biol. 2005 Dec;12(12):1064-71. doi: 10.1038/nsmb1023. Epub 2005 Nov 20.
The histone variant H2AZ is incorporated preferentially at specific locations in chromatin to modulate chromosome functions. In Saccharomyces cerevisiae, deposition of histone H2AZ is mediated by the multiprotein SWR1 complex, which catalyzes ATP-dependent exchange of nucleosomal histone H2A for H2AZ. Here, we define interactions between SWR1 components and H2AZ, revealing a link between the ATPase domain of Swr1 and three subunits required for the binding of H2AZ. We discovered that Swc2 binds directly to and is essential for transfer of H2AZ. Swc6 and Arp6 are necessary for the association of Swc2 and for nucleosome binding, whereas other subunits, Swc5 and Yaf9, are required for H2AZ transfer but neither H2AZ nor nucleosome binding. Finally, the C-terminal alpha-helix of H2AZ is crucial for its recognition by SWR1. These findings provide insight on the initial events of histone exchange.
组蛋白变体H2AZ优先整合于染色质的特定位置以调节染色体功能。在酿酒酵母中，组蛋白H2AZ的沉积由多蛋白SWR1复合物介导，该复合物催化核小体组蛋白H2A与H2AZ的ATP依赖性交换。在此，我们确定了SWR1组分与H2AZ之间的相互作用，揭示了Swr1的ATP酶结构域与H2AZ结合所需的三个亚基之间的联系。我们发现Swc2直接结合H2AZ并对其转移至关重要。Swc6和Arp6对于Swc2的缔合以及核小体结合是必需的，而其他亚基Swc5和Yaf9是H2AZ转移所必需的，但对H2AZ和核小体结合均无作用。最后，H2AZ的C末端α螺旋对于其被SWR1识别至关重要。这些发现为组蛋白交换的起始事件提供了见解。
