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2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin receptors regulate transcription of the cytochrome P 1 ‐450 gene
Author(s) -
Durrin Linda K.,
Jones Phillip B. C.,
Fisher Joan M.,
Galeazzi Donna R.,
Whitlock James P.
Publication year - 1987
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240350208
Subject(s) - aryl hydrocarbon receptor , enhancer , aryl hydrocarbon receptor nuclear translocator , transcription (linguistics) , receptor , cytochrome , transcription factor , gene , microbiology and biotechnology , chemistry , biology , gene expression , biochemistry , enzyme , linguistics , philosophy
Abstract The environmental contaminant 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) dioxin, produces a diverse set of biological responses which, in some cases, reflects the altered expression of specific genes. An intracellular receptor protein binds TCDD saturably and with high affinity and mediates several of TCDD's biological effects. In mouse hepatoma cells, TCDD induces aryl hydrocarbon hydroxylase activity by activating the transcription of the cytochrome P 1 ‐450 gene. Studies of receptor‐defective variant cells indicate that the activation of cytochrome P 1 ‐450 gene transcription requires functional TCDD receptors. Analysis of the DNA that flanks the 5′‐end of the mouse cytochrome P 1 ‐450 gene reveals at least three control regions: a promoter, an inhibitory element, and a dioxin‐responsive element (DRE). Therefore, expression of the cytochrome P 1 ‐450 gene represents a balance between negative and positive control. The DRE contains two discrete, non‐overlapping DNA domains that respond to TCDD. Each TCDD‐responsive domain acts independently of the other, each requires TCDD receptors for function, and each has the properties of a transcriptional enhancer. For example, the function of the DREs is relatively independent of both their location and their orientation with respect to the promoter. Together, the DREs and the TCDD‐receptor complex constitute a dioxin‐responsive enhancer system. Exposure of cells to TCDD results in the protection of a specific DNA domain from exonuclease digestion. This protection requires TCDD receptors. The protected domain maps to a DRE. This observation implies that the TCDD‐receptor complex interacts with the DRE to activate the transcription of the cytochrome P 1 ‐450 gene.