Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss

Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss
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DOI:
10.1016/j.cell.2005.08.036
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发表时间:
2005-10-21
期刊:
影响因子:
64.5
通讯作者:
Cairns, BR
Cairns, BR
中科院分区:
生物学1区
文献类型:
--
作者:
Zhang, HY;Roberts, DN;Cairns, BR

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组蛋白变体有助于使染色质区域特化;然而,它们对转录调控的影响在很大程度上是未知的。在此,我们确定了酵母组蛋白H2A变体Htz1在全基因组的定位和动态变化。Htz1定位于数百个受抑制的/基础的RNA聚合酶II(Pol II)启动子,并且更倾向于无TATA框的启动子。特定的Htz1沉积需要SWR1复合物,该复合物在很大程度上与Htz1共定位。Htz1的占位与特定的组蛋白修饰相关,并且Htz1的沉积部分依赖于Gcn5(一种组蛋白乙酰转移酶)和Bdf1(一种结合乙酰化组蛋白的SWR1复合物成员)。生长条件的改变导致Htz1从激活的启动子显著地重新分布到受抑制的/基础的启动子。此外,Htz1促进基因的完全激活,但通常不影响基因抑制。重要的是,在体外纯化的染色质中,在H2A和H3仍然结合的条件下,Htz1会释放。我们认为,含有Htz1的核小体沉积在受抑制的/基础的启动子处,但通过其易于丢失的特性促进激活,从而有助于暴露启动子DNA。
Histone variants help specialize chromatin regions; however, their impact on transcriptional regulation is largely unknown. Here, we determined the genome-wide localization and dynamics of Htz1, the yeast histone H2A variant. Htz1 localizes to hundreds of repressed/basal Pol II promoters and prefers TATA-less promoters' Specific Htz1 deposition requires the SWR1 complex, which largely colocalizes with Htz1. Htz1 occupancy correlates with particular histone modifications, and Htz1 deposition is partially reliant on Gcn5 (a histone acetyltransferase) and Bdf1, an SWR1 complex member that binds acetylated histones. Changes in growth conditions cause a striking redistribution of Htz1 from activated to repressed/basal promoters. Furthermore, Htz1 promotes full gene activation but does not generally impact repression. Importantly, Htz1 releases from purified chromatin in vitro under conditions where H2A and H3 remain associated. We suggest that Htz1 bearing nucleosomes are deposited at repressed/basal promoters but facilitate activation through their susceptibility to loss, thereby helping to expose promoter DNA.