title: Systematic characterisation of the rat and human CYP24A1 promoter.
abstract: The biologically active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) ligands VDR (vitamin D receptor) and binds to the vitamin D response element (VDRE) located within target genes to regulate their transcription. Previously we showed that 1,25D-mediated rat CYP24A1 induction via the two critical VDREs is dependent on a short stretch of nucleotides called vitamin D stimulating element (VSE), located approximately 30bp upstream of VDRE-1 in the rat CYP24A1 promoter. We have now undertaken systematic analysis of the human CYP24A1 and rat CYP24A1 promoters to determine if the VSE is present in the human promoter. Using electrophoretic mobility shift and dual-luciferase reporter assays, we show that the VSE is absent in the human CYP24A1 promoter. In addition, we show that 1,25D-mediated induction of human CYP24A1 is dependant upon a promoter region spanning nucleotides -470 to -392 of the human CYP24A1 promoter.
authors.affiliation: Breast Cancer Genetics Group, Discipline of Medicine, University of Adelaide and Hanson Institute, SA Pathology, Frome Road, Adelaide, SA 5000, Australia. raman.sharma@adelaide.edu.au
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.forename: D N
authors.initials: DN
authors.lastname: Iachini
authors.forename: P M
authors.initials: PM
authors.lastname: Neilsen
authors.forename: J
authors.initials: J
authors.lastname: Kaplan
authors.forename: J
authors.initials: J
authors.lastname: Michalakas
authors.forename: P H
authors.initials: PH
authors.lastname: Anderson
authors.forename: B K
authors.initials: BK
authors.lastname: May
authors.forename: H A
authors.initials: HA
authors.lastname: Morris
authors.forename: D F
authors.initials: DF
authors.lastname: Callen
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013250:Steroid Hydroxylases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D030181:Vitamin D Response Element / Q000502:physiology; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D018167:Receptors, Calcitriol; D002762:Cholecalciferol; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; C585551:Cyp24a1 protein, rat; D065668:Vitamin D3 24-Hydroxylase