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组蛋白变体H2A.Z/Htz1p在TBP募集、染色质动力学及油酸应答基因的调控表达中的作用

Role of the histone variant H2A.Z/Htz1p in TBP recruitment, chromatin dynamics, and regulated expression of oleate-responsive genes.

作者信息

Wan Yakun, Saleem Ramsey A, Ratushny Alexander V, Roda Oriol, Smith Jennifer J, Lin Chan-Hsien, Chiang Jung-Hsien, Aitchison John D

机构信息

Institute for Systems Biology, 1441 N 34th St., Seattle, WA 98103, USA.

出版信息

Mol Cell Biol. 2009 May;29(9):2346-58. doi: 10.1128/MCB.01233-08. Epub 2009 Mar 9.

Abstract

The histone variant H2A.Z (Htz1p) has been implicated in transcriptional regulation in numerous organisms, including Saccharomyces cerevisiae. Genome-wide transcriptome profiling and chromatin immunoprecipitation studies identified a role for Htz1p in the rapid and robust activation of many oleate-responsive genes encoding peroxisomal proteins, in particular POT1, POX1, FOX2, and CTA1. The Swr1p-, Gcn5p-, and Chz1p-dependent association of Htz1p with these promoters in their repressed states appears to establish an epigenetic marker for the rapid and strong expression of these highly inducible promoters. Isw2p also plays a role in establishing the nucleosome state of these promoters and associates stably in the absence of Htz1p. An analysis of the nucleosome dynamics and Htz1p association with these promoters suggests a complex mechanism in which Htz1p-containing nucleosomes at fatty acid-responsive promoters are disassembled upon initial exposure to oleic acid leading to the loss of Htz1p from the promoter. These nucleosomes reassemble at later stages of gene expression. While these new nucleosomes do not incorporate Htz1p, the initial presence of Htz1p appears to mark the promoter for sustained gene expression and the recruitment of TATA-binding protein.

摘要

组蛋白变体H2A.Z(Htz1p)在包括酿酒酵母在内的众多生物体的转录调控中发挥作用。全基因组转录组分析和染色质免疫沉淀研究表明,Htz1p在快速、强劲激活许多编码过氧化物酶体蛋白的油酸反应基因中发挥作用,特别是POT1、POX1、FOX2和CTA1。在这些启动子处于抑制状态时,Htz1p与Swr1p、Gcn5p和Chz1p依赖的结合似乎为这些高度可诱导启动子的快速、强表达建立了一种表观遗传标记。Isw2p在建立这些启动子的核小体状态中也发挥作用,并且在没有Htz1p的情况下稳定结合。对这些启动子的核小体动力学和Htz1p结合的分析表明,存在一种复杂机制,其中脂肪酸反应启动子上含有Htz1p的核小体在最初暴露于油酸时会解体,导致Htz1p从启动子上丢失。这些核小体在基因表达的后期重新组装。虽然这些新的核小体不包含Htz1p,但Htz1p的最初存在似乎标记了启动子以实现持续的基因表达和TATA结合蛋白的募集。

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