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

G. Antonio Candeliere, Peter W. Jurutka, Mark R. Haussler, René St-Arnaud

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

The hormonal form of vitamin D, 1α,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 of 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 α 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.

Original languageEnglish (US)
Pages (from-to)584-592
Number of pages9
JournalMolecular and cellular biology
Volume16
Issue number2
DOIs
StatePublished - Feb 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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