Regulatory DNA elements localized remotely upstream from the drug-metabolizing cytochrome P450 gene. Nucleic Acids Res

we have investigated regulatory DNA elements in the expres-sion of the drug metabolizing P-450c gene of rats. Aftar combin-ing the 51 flanking and upstream untranslated regions of the isolated P-450c gene with structural gene for chloramphenicol acetyltransferase (CAT), the fusion genes were transfected into cultured cells (Kepa-1 and L cells) for the assay of transient expression of CAT activity. CAT activity was expressed inducibly in response to 3-methylcholanthrene only in Kepa-1 cells. At least three regions containing regulatory DNA elements were indentified; one, which is present in the sequence from-44b to-0.2kb immediately upstream of the TATA box, functions in the basal level of transcription, and the'other two which were located in the sequence from-0.8kb to-1.0kb and from-1.0kb to-6.3kb, enhance in combination, transcription in response to inducers in a manner independent of their orientation