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Type: Journal article
Title: Transcriptional Sygernism Between Vitamin D-Rsponsive Elements in the Rat 25-Hyroxyvitamin D-3 24-Hydroxylase (CYP24) Promotor
Author: Kerry, D.
Dwivedi, P.
Morris, H.
Omdahl, J.
May, B.
Citation: Journal of Biological Chemistry, 1996; 271(47):29715-29721
Issue Date: 1996
ISSN: 0021-9258
Abstract: Transcription of the CYP24 gene is induced by 1,25-(OH)2D3 through a vitamin D receptor-dependent process. The functional activities of three possible vitamin D response elements (VDREs), located on the antisense strand of the rat CYP24 promoter, were investigated by transient expression of native and mutant promoter constructs in COS-1, JTC-12, and ROS 17/2.8 cells. A putative VDRE with a half-site spacing of 6 base pairs at -249/-232 (VDRE-3) did not contribute to 1,25-(OH)2D3 induced expression in the native promoter, although activity has been reported when the element was fused to the heterologous thymidine kinase promoter. Two VDREs with half-site spacings of 3 base pairs at -150/-136 and -258/-244 (VDRE-1 and VDRE-2, respectively), showed transcriptional synergism in COS-1 cells when treated with 1,25-(OH)2D3 (10(-7) to 10(-11) M). The contribution of both VDREs was hormone-concentration dependent from 10(-10) to 10(-12) M, with VDRE-1 demonstrating greatest sensitivity to 1,25-(OH)2D3. Transactivation by VDRE-1 was always greater than VDRE-2, but the converse was observed for the binding of vitamin D receptor-retinoid X receptor complex by each VDRE in gel mobility shift assays. The synergy observed between VDRE-1 and VDRE-2 may have important implications in cellular responses to different circulating levels of 1,25-(OH)2D3.
Keywords: Cell Line
Cytochrome P-450 Enzyme System
Steroid Hydroxylases
Vitamin D
Nuclear Proteins
Mutagenesis, Site-Directed
Transcription, Genetic
Gene Expression Regulation, Enzymologic
Protein Binding
Promoter Regions, Genetic
Vitamin D3 24-Hydroxylase
DOI: 10.1074/jbc.271.47.29715
Appears in Collections:Aurora harvest 7
Biochemistry publications

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