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

Academic Article

Abstract

  • We have identified a novel steroid hormone response element in the avian beta3 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 RAR-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.
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    Published In

    Keywords

  • Animals, Antigens, CD, Base Sequence, Birds, Cholecalciferol, DNA Mutational Analysis, DNA-Binding Proteins, Gene Expression Regulation, Integrin beta3, Molecular Sequence Data, Platelet Membrane Glycoproteins, Promoter Regions, Genetic, Protein Binding, RNA, Messenger, Receptors, Calcitriol, Receptors, Retinoic Acid, Retinoid X Receptors, Structure-Activity Relationship, Transcription Factors, Transcription, Genetic, Tretinoin
  • Digital Object Identifier (doi)

    Author List

  • Cao X; Teitelbaum SL; Zhu HJ; Zhang L; Feng X; Ross FP
  • Start Page

  • 20650
  • End Page

  • 20654
  • Volume

  • 271
  • Issue

  • 34