Activation of transcription as a general mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin action

✍ Scribed by Joan M. Fisher; Keith W. Jones; James P. Whitlock Jr.

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 534 KB
• Volume: 1
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.2940010403

✦ Synopsis

We studied the response t o 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) of mouse hepatoma cells that contain a single, integrated copy o f a chimeric gene under the control of a dioxin-responsive DNA domain, which was originally associated with the cytochrome P450/A 7 gene. Our findings indicate that TCDD increases the RNA polymerase Il-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 t o 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 o f the cytochrome P4501AI gene. Therefore, in principle, the receptor-enhancer system represents a mechanism by which numerous genes can respond to aromatic hydrocarbons in the environment.