A Composite Element Binding the Vitamin D Receptor, Retinoid X Receptor α, and a Member of the CTF/NF-1 Family of Transcription Factors Mediates the Vitamin D Responsiveness of the c-fos Promoter
| Autor: | René St-Arnaud, Peter W. Jurutka, M R Haussler, G A Candeliere |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Receptors
Retinoic Acid DNA Mutational Analysis Molecular Sequence Data Response element Biology Calcitriol receptor Bone and Bones Calcitriol Vitamin D Response Element Tissue Distribution Promoter Regions Genetic Molecular Biology Transcription factor Cells Cultured Binding Sites Osteoblasts Base Sequence Retinoid X receptor alpha Ccaat-enhancer-binding proteins Cell Biology Molecular biology VDRE DNA-Binding Proteins NFI Transcription Factors Retinoid X Receptors Gene Expression Regulation Nuclear receptor CCAAT-Enhancer-Binding Proteins Receptors Calcitriol Proto-Oncogene Proteins c-fos Research Article Protein Binding Signal Transduction Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 16:584-592 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.16.2.584 |
| Popis: | The hormonal form of vitamin D, 1 alpha,25-dihydroxyvitamin D3 [1,25- (OH)2D3], transiently stimulates the transcription of the c-fos proto-oncogene in osteoblastic cells. We have identified and characterized a vitamin D response element (VDRE) in the promoter of c-fos. The 1,25-(OH)2D3-responsive region was delineated between residues -178 and -144 upstream of the c-fos transcription start site. A mutation that inhibited binding to the sequence concomitantly abolished 1,25-(OH)2D3-induced transcriptional responsiveness; similarly, cloning to the site upstream of a heterologous promoter conferred copy-number-dependent vitamin D responsiveness to a reporter gene, demonstrating that we have identified a functional response element. The structure of the c-fos VDRE was found to be unusual. Mutational analysis revealed that the c-fos VDRE does not conform to the direct repeat configuration in which hexameric core-binding sites are spaced by a few nucleotide residues. In contrast, the entire 36-bp sequence was essential for binding. We identified the vitamin D receptor and the retinoid X receptor alpha as components of the complex that bound the c-fos VDRE. However, our results also show that a putative CCAAT-binding transcription factor/nuclear factor 1 (CTF/NF-1) family member bound the response element in conjunction with the nuclear hormone receptors. The expression of this CTF/NF-1 family member appeared restricted to bone cells. These data hint at new molecular mechanisms of action for vitamin D. |
| Databáze: | OpenAIRE |
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