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Activation of transcription as a general mechanism of 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin action
Author(s) -
Fisher Joan M.,
Jones Keith W.,
Whitlock James P.
Publication year - 1989
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940010403
Subject(s) - enhancer , biology , transcription (linguistics) , gene , transcription factor , rna polymerase ii , microbiology and biotechnology , gene expression , dna , cytochrome , regulation of gene expression , reporter gene , promoter , genetics , biochemistry , enzyme , linguistics , philosophy
We studied the response to 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD) of mouse hepatoma cells that contain a single, integrated copy of a chimeric gene under the control of a dioxin‐responsive DNA domain, which was originally associated with the cytochrome P450IA1 gene. Our findings indicate that TCDD increases the RNA polymerase II‐catalyzed transcription rate of the chimeric gene and that the transcripts are initiated at the correct promoter. Therefore, the dioxin‐responsive DNA operates as a bona fide transcriptional enhancer. Other studies imply that the Ah receptor mediates the transcriptional response to TCDD. Our results indicate that the Ah receptor‐dependent, dioxin‐responsive enhancer can activate transcription when in a regulatory context and in a chromosomal location different from those of the cytochrome P450IA1 gene. Therefore, in principle, the receptor‐enhancer system represents a mechanism by which numerous genes can respond to aromatic hydrocarbons in the environment.