Role of distal upstream sequence in vitamin D-induced expression of human CYP24 gene.
The level of CYP24 mRNA in cultured human fibroblasts increases up to 20,000-fold in response to 1,25-dihydroxyvitamin D(3). Two vitamin D-responsive elements (VDREs) located immediately upstream of the CYP24 gene are primarily responsible for the induction. We studied roles of other regions in the 5'-flanking sequence of this gene. A series of deletion constructs between nucleotides -1918 and +209 of the gene were examined for their promoter activities employing the luciferase reporter assay. We found that the VDREs were not sufficient to account for the extent of induction. The sequence between nucleotides -548 and -294, which is located immediately upstream of the VDREs and includes three potential Sp1 sites, acted synergistically with the VDREs for the induction. Further upstream sequence and the 5'-untranslated region did not appear to play a major role in the vitamin D response.
Tashiro
Katsuhisa
K
Molecular Biology Laboratory, Department of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka, Shobara, Hiroshima 727-0023, Japan.
Ishii
Chieko
C
Ryoji
Masaru
M
D024506:5' Flanking Region; D001665:Binding Sites; D002478:Cells, Cultured; D004790:Enzyme Induction; D005347:Fibroblasts / Q000201:enzymology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology; D030181:Vitamin D Response Element; D065668:Vitamin D3 24-Hydroxylase
D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase