Activation of transcription as a general mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin action.
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.
Fisher
J M
JM
Department of Pharmacology, Stanford University School of Medicine, California.
Jones
K W
KW
Whitlock
J P
JP
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002678:Chimera; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D004147:Dioxins / Q000494:pharmacology*; D004790:Enzyme Induction; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000235:genetics*; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D015183:Restriction Mapping; D014158:Transcription, Genetic / Q000187:drug effects*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D015500:Chloramphenicol O-Acetyltransferase