Denison M S, Fisher J M, Whitlock J P
Department of Pharmacology, Stanford University School of Medicine, California 94305.
J Biol Chem. 1988 Nov 25;263(33):17221-4.
The environmental contaminant 2,3,7,8-tetra-chlorodibenzo-p-dioxin produces its biological effects by binding to an intracellular protein (the Ah receptor). The dioxin-Ah receptor complex activates cytochrome P1-450 gene transcription by interacting with dioxin-responsive enhancers. Here, we report that the dioxin-Ah receptor complex binds to DNA containing the "core" sequence 5'-TA/TGCGTG-3', which is present in each of three receptor-dependent enhancers. Functional analyses indicate that binding of the liganded Ah receptor to the core sequence fails to generate an active enhancer and that nucleotides flanking the core sequence must contribute to enhancer function and dioxin action.
环境污染物2,3,7,8-四氯二苯并对二恶英通过与一种细胞内蛋白质(芳烃受体)结合产生其生物学效应。二恶英-芳烃受体复合物通过与二恶英反应性增强子相互作用激活细胞色素P1-450基因转录。在此,我们报告二恶英-芳烃受体复合物与含有“核心”序列5'-TA/TGCGTG-3'的DNA结合,该序列存在于三个受体依赖性增强子中的每一个中。功能分析表明,配体化的芳烃受体与核心序列的结合未能产生活性增强子,并且核心序列两侧的核苷酸必须有助于增强子功能和二恶英作用。