Role of coactivators in transcriptional activation by the aryl hydrocarbon receptor
Role of coactivators in transcriptional activation by the aryl hydrocarbon receptor
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DOI：
10.1016/j.abb.2004.09.031
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发表时间：
2005-01-15
影响因子：
3.9
通讯作者：
Hankinson, O
中科院分区：
文献类型：
--
作者：
Hankinson, O
芳烃受体（AHR）介导多种环境污染物的致癌和其它毒性效应，包括2，37，8-四氯二苯并对二恶英（TCDD）和一些多环芳烃（PAH）。在大多数情况下，如果不是所有的情况下，这些有害的影响取决于由配体结合的AHR影响的基因转录的调节。TCDD毒性所需的反应基因尚未确定。然而，Cyp 1a 1的诱导是已知的代表一个重要的事件，在多环芳烃的毒性。此外，Cyp 1a 1基因为研究AHR的基因转录机制提供了一个模型系统。本文综述了转录辅激活蛋白在AHR配体诱导Cyp 1a 1表达中的作用。辅激活因子在诱导后与基因物理结合，并在位于5 '增强子元件的AHR分子和位于基因启动子的一般转录因子之间提供桥梁。强调了内源Cyp 1a 1基因在其自然染色体背景中的研究。最近发展的几种新的实验技术，包括染色质免疫沉淀（ChIP）测定，RNA干扰和实时PCR提供了一个重大推动这样的研究。未来的研究方向进行了讨论。由于辅激活因子表达或活性的变化可能导致对AHR配体反应的个体间差异，并且也可能是发育期间和成年期对此类配体敏感性的组织特异性差异的基础，因此辅激活因子在AHR转录激活中的作用构成了非常重要的研究领域。(C)2004年爱思唯尔公司All rights reserved.
The aryl hydrocarbon receptor (AHR) mediates the carcinogenic and other toxic effects of a variety of environmental pollutants, including 2,37,8-tetrachlorodibenzo-p-dioxin (TCDD), and some polycyclic aromatic hydrocarbons (PAHs). In most if not all cases, these deleterious effects depend upon modulation of gene transcription effected by the ligand-bound AHR. The responsive genes required for toxicity of TCDD have yet to be defined. However, induction of Cyp1a1 is known to represent a significant event in the toxicity of PAHs. Furthermore, the Cyp1a1 gene provides a model system for studying the mechanism of gene transcription by AHR. This review discusses the roles of transcriptional coactivator proteins in induction of Cyp1a1 by AHR ligands. Coactivators physically associate with the gene upon induction, and provide a bridge between AHR molecules, located at 5'enhancer elements, and general transcription factors, located at the promoter of the gene. Studies oil the endogenous Cyp1a1 gene in its natural chromosomal setting are emphasized. The recent development of several new experimental techniques including the chromatin immunoprecipitation (ChIP) assay, RNA interference, and real-time PCR has provided a major boost to such studies. Future directions for research are also discussed. Since variations in coactivator expression or activity may result ill inter-individual differences in response to AHR ligands, and may also underlie tissue-specific differences in sensitivity to such ligands during development, and in adulthood, the role of coactivators in transcriptional activation by A H R Constitutes a very important area of research. (C) 2004 Elsevier Inc. All rights reserved.