Competition for a unique response element mediates retinoic acid inhibition of vitamin D3-stimulated transcription

Xu Cao, Steven L. Teitelbaum, Hui Jun Zhu, Liming Zhang, Xu Feng, F. Patrick Ross

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

We have identified a novel steroid hormone response element in the avian β3 integrin promoter. This sequence, comprising three hexameric direct repeat half-sites separated by nine and three nucleotides binds vitamin D receptor (VDR)-retinoid X receptor (RXR) and retinoic acid receptor (RAR)- RXR heterodimers. VDR-RXR binds direct repeats separated by three base pairs, and HAR-RXR recognizes half-sites separated by nine bases, whereas the central half-site interacts with both heterodimers. Retinoic acid and 1,25- dihydroxyvitamin D3 activate both a genomic fragment including the transcriptional start site and an oligonucleotide containing the three repeats, linked to a heterologous promoter. Co-addition of the steroids produces neither synergy nor an additive effect; rather the result equals that for retinoic acid alone. Scatchard analysis demonstrates that RAR-RXR has greater affinity than VDR-RXR for the composite element. Based on these findings we propose a model in which there is specific, polarity-defined binding of VDR-RXR and RAR-RXR to three half-sites, which form two overlapping steroid response elements, with the central half-site common to both. Our results identify a novel mechanism by which one steroid hormone can modulate the activity of a second, by competing for a shared half-site in a composite response element.

Original languageEnglish (US)
Pages (from-to)20650-20654
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number34
DOIs
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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