來自美國國立衛(wèi)生院癌癥研究所（NCI）的研究人員解析了一種重要的組蛋白變體：H2A.Z的相關(guān)作用機(jī)制,，從而為進(jìn)一步解析基因表達(dá)啟動子調(diào)控提供了新的依據(jù)。領(lǐng)導(dǎo)這一研究的是美國國家科學(xué)院院士,，華人科學(xué)家吳以仲,。
染色質(zhì)結(jié)構(gòu)的基本重復(fù)單元：核小體是由組蛋白八聚體 (由4種核心組蛋白H2A,、H2B、H3和H4的各兩個單體構(gòu)成) 以及纏繞在其上的DNA序列構(gòu)成的,。組蛋白變體是相對于染色體中的常規(guī)組蛋白而言的,，是特殊狀態(tài)的染色體所需的組蛋白類型。處于不同狀態(tài)的染色體需要相應(yīng)的組蛋白變體維持特定的結(jié)構(gòu),，以完成其生物學(xué)功能,。
組蛋白H2A的變體H2A.Z就是一種普遍存在于真核生物細(xì)胞中，在基因的表達(dá)過程中發(fā)揮著重要作用的組蛋白,，這種蛋白參與了基因表達(dá)的啟動過程,，通過SWR1復(fù)合結(jié)構(gòu)調(diào)控基因表達(dá)。
在這篇文章中,，研究人員發(fā)現(xiàn)酵母中啟動子近端的核小體H2A.Z存在不同的形式,，包含有1個，2個或者沒有H2A.Z,。并且通過進(jìn)一步的實驗,，研究人員也發(fā)現(xiàn)了SWR1在H2A.Z，H2A.Z-H2B等替換過程中的催化作用,，這些研究為進(jìn)一步解析基因表達(dá)啟動子調(diào)控提供了新的依據(jù),。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
