Binding of TATA binding protein to a naturally positioned nucleosome is facilitated by histone acetylation
Binding of TATA binding protein to a naturally positioned nucleosome is facilitated by histone acetylation
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DOI：
10.1128/mcb.21.4.1404-1415.2001
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发表时间：
2001-02-01
影响因子：
5.3
通讯作者：
Hansen, U
中科院分区：
文献类型：
--
作者：
Sewack, GF;Ellis, TW;Hansen, U
人雌激素响应性pS2启动子的TATA序列在体内与旋转和旋转定位的核小体（NUCT）复合。使用染色质免疫沉淀试验，我们证明，TATA结合蛋白（TBP）不检测与此基因组结合位点在MCF-7细胞中的转录刺激的情况下相互作用。这些细胞的雌激素刺激导致包含NUC T和TATA序列的pS2染色质内的组蛋白H3和H4的超乙酰化。同时，TBP与pS2启动子区结合。使用pS2启动子上的体内组装核小体阵列在体外分析了组蛋白超乙酰化与TBP结合之间的关系。染色质处于其基础状态时，TBP与NUC T边缘的pS2 TATA序列的结合受到严重限制，与我们的体内数据一致。核心组蛋白的乙酰化促进了TBP与核小体TATA序列的结合。因此，我们证明了一个特定的，功能性的结果诱导组蛋白乙酰化在一个天然的启动子是减轻核小体介导的抑制TBP的结合。我们的数据支持组蛋白乙酰化在基因组启动子核受体转录激活中的基本作用，并提供了一种从染色质模板快速可逆转录激活的一般机制。
The TATA sequence of the human, estrogen-responsive pS2 promoter is complexed in vivo with a rotationally and translationally positioned nucleosome (NUC T). Using a chromatin immunoprecipitation assay, we demonstrate that TATA binding protein (TBP) does not detectably interact with this genomic binding site In MCF-7 cells in the absence of transcriptional stimuli. Estrogen stimulation of these cells results in hyperacetylation of both histones H3 and H4 within the pS2 chromatin encompassing NUC T and the TATA sequence. Concurrently, TBP becomes associated with the pS2 promoter region. The relationship between histone hyperacetylation and the binding of TBP was assayed in vitro using an in vivo-assembled nucleosomal array over the pS2 promoter. With chromatin in its basal state, the binding of TBP to the pS2 TATA sequence at the edge of NUC T was severely restricted, consistent with our in vivo data. Acetylation of the core histones facilitated the binding of TBP to this nucleosomal TATA sequence. Therefore, we demonstrate that one specific, functional consequence of induced histone acetylation at a native promoter is the alleviation of nucleosome-mediated repression of the binding of TBP. Our data support a fundamental role for histone acetylation at genomic promoters in transcriptional activation by nuclear receptors and provide a general mechanism for rapid and reversible transcriptional activation from a chromatin template.