Cell：组蛋白变体H2A.Z的相关作用机制解析

来自美国国立卫生院癌症研究所（NCI）的研究人员解析了一种重要的组蛋白变体：H2A.Z的相关作用机制，从而为进一步解析基因表达启动子调控提供了新的依据。领导这一研究的是美国国家科学院院士，华人科学家吴以仲。

染色质结构的基本重复单元：核小体是由组蛋白八聚体 (由4种核心组蛋白H2A、H2B、H3和H4的各两个单体构成) 以及缠绕在其上的DNA序列构成的。组蛋白变体是相对于染色体中的常规组蛋白而言的，是特殊状态的染色体所需的组蛋白类型。处于不同状态的染色体需要相应的组蛋白变体维持特定的结构，以完成其生物学功能。

组蛋白H2A的变体H2A.Z就是一种普遍存在于真核生物细胞中，在基因的表达过程中发挥着重要作用的组蛋白，这种蛋白参与了基因表达的启动过程，通过SWR1复合结构调控基因表达。

在这篇文章中，研究人员发现酵母中启动子近端的核小体H2A.Z存在不同的形式，包含有1个，2个或者没有H2A.Z。并且通过进一步的实验，研究人员也发现了SWR1在H2A.Z，H2A.Z-H2B等替换过程中的催化作用，这些研究为进一步解析基因表达启动子调控提供了新的依据。

生物谷推荐原文出处：

Cell doi :10.1016/j.cell.2010.10.019

Stepwise Histone Replacement by SWR1 Requires Dual Activation with Histone H2A.Z and Canonical Nucleosome

Highlights

Nucleosomes at yeast promoters are heterogeneous for H2A and H2A.Z histones

SWR1 generates homotypic H2A.Z nucleosomes in a stepwise, unidirectional manner

H2A-containing nucleosome and H2A.Z-H2B dimer together hyperstimulate the SWR1 ATPase

These substrates also specifically activate histone replacement by SWR1

Summary

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 zero 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.