Stepwise histone replacement by SWR1 requires dual activation with histone H2A.Z and canonical nucleosome.
Stepwise histone replacement by SWR1 requires dual activation with histone H2A.Z and canonical nucleosome.
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SWR1逐步替代组蛋白需要组蛋白H2A.Z和规范核小体双重激活。
DOI：
10.1016/j.cell.2010.10.019
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发表时间：
2010-11-24
期刊：
影响因子：
64.5
通讯作者：
Wu C
中科院分区：
文献类型：
--
作者：
Luk E;Ranjan A;Fitzgerald PC;Mizuguchi G;Huang Y;Wei D;Wu C
含组蛋白变异体H_2A.Z的核小体存在于大多数真核启动子中。这种掺入是由保守的SWR1复合体介导的，它以一种依赖于ATP的方式将标准核小体中的组蛋白H_2A替换为H_2A.Z。在这里，我们表明在酿酒酵母中，启动子近端的核小体对H_2A.Z具有高度的异质性，大量的核小体含有一个、两个或不含H_2A.Z分子。在体外，SWR1催化的H2A.Z置换以循序渐进和单向的方式发生，一次一个H2A.Z-H2B二聚体，产生异型核小体作为中间产物，同型H_2A.Z核小体作为最终产物。含有H_2A的核小体可以特异性地刺激SWR_1的ATPase活性，而不会导致组蛋白H_2A被驱逐。值得注意的是，进一步加入游离的H_2A.Z-H_2B二聚体会导致ATPase活性的过度刺激、核小体H_2A-H_2B的驱逐和H_2A_Z-H_2B的沉积。这些结果表明，含有H_2A的核小体和作为SWR1的效应物和底物的游离H_2A-Z-H_2B二聚体的结合控制了置换反应的特异性和结果。
Histone variant H2A.Z-containing nucleosomes are incorporated at most eukaryotic promoters. This incorporation is mediated by the conserved SWR1 complex, which replaces histone H2A in canonical nucleosomes with H2A.Z in an ATP-dependent manner. Here, we show that promoter-proximal nucleosomes are highly heterogeneous for H2A.Z in Saccharomyces cerevisiae, with substantial representation of nucleosomes containing one, two, or no H2A.Z molecules. SWR1-catalyzed H2A.Z replacement in vitro occurs in a stepwise and unidirectional fashion, one H2A.Z-H2B dimer at a time, producing heterotypic nucleosomes as intermediates and homotypic H2A.Z nucleosomes as end products. The ATPase activity of SWR1 is specifically stimulated by H2A-containing nucleosomes without ensuing histone H2A eviction. Remarkably, further addition of free H2A.Z-H2B dimer leads to hyperstimulation of ATPase activity, eviction of nucleosomal H2A-H2B and deposition of H2A.Z-H2B. These results suggest that the combination of H2A-containing nucleosome and free H2A.Z-H2B dimer acting as both effector and substrate for SWR1 governs the specificity and outcome of the replacement reaction.
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影响因子：
13.8
作者：
Das, Chandrima;Tyler, Jessica K.;Churchill, Mair E. A.
通讯作者：
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影响因子：
4.8
作者：
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DOI：
10.1007/bf00282226
发表时间：
1994-12-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
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作者：
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通讯作者：
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作者：
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作者：
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通讯作者：
Rando, Oliver J.