Abstract
Gene transfer experiments indicate that induction by the peroxisome proliferators, clofibric acid and WY-14,643, of luciferase expression driven by the promoter and 5'-flanking sequences of the rabbit cytochrome P450 4A6 gene (CYP4A6) is dependent on cotransfection of expression plasmids for the peroxisome proliferator-activated receptor, PPAR. Activation by PPAR is observed in the absence of the inducers. However, a mutant, PPAR-G (Glu282----Gly) activated luciferase expression only in the presence of peroxisome proliferators. Deletion analysis has localized a response element to a 34-base pair segment located 677 base pairs upstream of the CYP4A6 transcription start site that is similar to an element that regulates the response of the rat fatty acyl-CoA oxidase gene to peroxisome proliferators and that binds PPAR.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Base Sequence
-
Clofibric Acid / pharmacology*
-
Cloning, Molecular
-
Cytochrome P-450 CYP4A
-
Cytochrome P-450 Enzyme System / biosynthesis
-
Cytochrome P-450 Enzyme System / genetics*
-
Cytochrome P-450 Enzyme System / metabolism
-
Enzyme Induction / drug effects
-
Mice
-
Microbodies / physiology
-
Mixed Function Oxygenases / biosynthesis
-
Mixed Function Oxygenases / genetics*
-
Mixed Function Oxygenases / metabolism
-
Molecular Sequence Data
-
Promoter Regions, Genetic
-
Receptors, Cell Surface / genetics*
-
Receptors, Cytoplasmic and Nuclear*
-
Regulatory Sequences, Nucleic Acid
-
Transcription Factors / genetics*
-
Transfection
Substances
-
Receptors, Cell Surface
-
Receptors, Cytoplasmic and Nuclear
-
Transcription Factors
-
Clofibric Acid
-
Cytochrome P-450 Enzyme System
-
Mixed Function Oxygenases
-
Cytochrome P-450 CYP4A