Control of Cytochrome P 1 -450 Gene Expression by Dioxin

Autor: James P. Whitlock, Phillip B. C. Jones, Donna R. Galeazzi, Joan M. Fisher
Rok vydání: 1985
Předmět:
Zdroj: Science. 227:1499-1502
ISSN: 1095-9203
0036-8075
DOI: 10.1126/science.3856321
Popis: The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may produce its effects by altering gene expression in susceptible cells. In mouse hepatoma cells, TCDD induces the transcription of the cytochrome P1-450 gene, whose product, aryl hydrocarbon hydroxylase, contributes both to the detoxification and to the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons. A DNA fragment containing sequences flanking the 5' end of the cytochrome P1-450 gene was isolated and analyzed. This DNA fragment contains a cis-acting control element with at least three functional domains: a putative promoter, an inhibitory domain upstream from the promoter that blocks its function, and a TCDD-responsive domain still farther (1265 to 1535 base pairs) upstream of the promoter. These findings, together with results from earlier studies, imply that transcription of the cytochrome P1-450 gene is under both positive and negative control by at least two trans-acting regulatory factors.
Databáze: OpenAIRE