Regulatory DNA elements localized remotely upstream from the drug-metabolizing cytochrome P-450c gene.
We have investigated regulatory DNA elements in the expression of the drug metabolizing P-450c gene of rats. After combining the 5' 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 (Hepa-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 Hepa-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.
Fujisawa-Sehara
A
A
Sogawa
K
K
Nishi
C
C
Fujii-Kuriyama
Y
Y
D000123:Acetyltransferases / Q000235:genetics; D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D005809:Genes, Regulator; D005818:Genetic Engineering; D008040:Genetic Linkage; D007739:L Cells; D008114:Liver Neoplasms, Experimental; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D051381:Rats; D014162:Transfection
D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D000123:Acetyltransferases; D015500:Chloramphenicol O-Acetyltransferase