The peroxisome proliferator-activated receptor mediates the induction of CYP4A6, a cytochrome P450 fatty acid omega-hydroxylase, by clofibric acid.
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.
Muerhoff
A S
AS
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037.
Griffin
K J
KJ
Johnson
E F
EF
D000818:Animals; D001483:Base Sequence; D002995:Clofibric Acid / Q000494:pharmacology*; D003001:Cloning, Molecular; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D051379:Mice; D008830:Microbodies / Q000502:physiology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D002995:Clofibric Acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A