Isolation and properties of the CYP2D25 promoter: transcriptional regulation by vitamin D3 metabolites.
Previous studies have suggested that hepatic production of 25-hydroxyvitamin D3 may be suppressed by 1alpha,25-dihydroxyvitamin D3. However, the molecular details of these observations have not been clarified. In the current study, the 5'-flanking DNA sequence of CYP2D25, a porcine microsomal vitamin D 25-hydroxylase, was isolated and analyzed. The CYP2D25 promoter contains a putative vitamin D response element (VDRE). The promoter activity was markedly suppressed by 1alpha,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 in presence of vitamin D receptor (VDR). The data suggest that VDR-mediated inhibition of 25-hydroxylase(s) by vitamin D3 metabolites at the transcriptional level may play an important role in the regulation of 25-hydroxyvitamin D3 production in liver and other tissues.
Ellfolk
Maria
M
Department of Pharmaceutical Biosciences, Division of Biochemistry, University of Uppsala, Box 578, S-751 23 Uppsala, Sweden.
Norlin
Maria
M
Wikvall
Kjell
K
D000818:Animals; D001483:Base Sequence; D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D013552:Swine; D014158:Transcription, Genetic / Q000187:drug effects*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism; D030181:Vitamin D Response Element
C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D002762:Cholecalciferol; D003577:Cytochrome P-450 Enzyme System