n-Alkane and clofibrate, a peroxisome proliferator, activate transcription of ALK2 gene encoding cytochrome P450alk2 through distinct cis-acting promoter elements in Candida maltosa.
The ALK2 gene, encoding one of the n-alkane-hydroxylating cytochromes P450 in Candida maltosa, is induced by n-alkanes and a peroxisome proliferator, clofibrate. Deletion analysis of this gene's promoter revealed two cis-acting elements-an n-alkane-responsive element (ARE2) and a clofibrate-responsive element (CRE2)-that partly overlap in sequence but have distinct functions. ARE2-mediated activation responded to n-alkanes but not to clofibrate and was repressed by glucose. CRE2-mediated activation responded to polyunsaturated fatty acids and steroid hormones as well as to peroxisome proliferators but not to n-alkanes, and it was not repressed by glucose. Both elements mediated activation by oleic acid. Mutational analysis demonstrated that three CCG sequences in CRE2 were critical to the activation by clofibrate as well as to the in vitro binding of a specific protein to this element. These findings suggest that ALK2 is induced by peroxisome proliferators and steroid hormones through a specific CRE2-mediated regulatory mechanism.
Kogure
Takahisa
T
Department of Biotechnology, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-8657, Japan.
Takagi
Masamichi
M
Ohta
Akinori
A
D000473:Alkanes / Q000378:metabolism*; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001483:Base Sequence; D002175:Candida / Q000235:genetics*; D002994:Clofibrate / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004252:DNA Mutational Analysis; D005656:Fungal Proteins / Q000096:biosynthesis*; D017353:Gene Deletion; D017930:Genes, Reporter; D005947:Glucose / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D020025:Peroxisome Proliferators / Q000378:metabolism* / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014158:Transcription, Genetic; D018911:Trinucleotide Repeats; D001616:beta-Galactosidase / Q000378:metabolism
D000473:Alkanes; D000924:Anticholesteremic Agents; D005656:Fungal Proteins; D020025:Peroxisome Proliferators; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; C499277:Alk2 protein, Candida; D001616:beta-Galactosidase; D002994:Clofibrate; D005947:Glucose