Nuclear receptor coactivators facilitate vitamin D receptor homodimer action on direct repeat hormone response elements

Endocrinology. 2000 Mar;141(3):1281-4. doi: 10.1210/endo.141.3.7441.


Vitamin D receptor (VDR) is a ligand-dependent transcription factor that regulates target gene expression. Although VDR forms stable heterodimer complex with retinoid X receptors (RXRs) on vitamin D-response elements (VDREs), it is still not clear whether VDR/RXR heterodimers are the only VDR complexes responsible for vitamin D-mediated gene transcription. In this report, we analyzed the effect of nuclear receptor coactivators (SRC-1 and TRAM-1) on VDR homodimer and VDR/RXR heterodimer formation by electrophoretic mobility shift assay. We found that VDR forms stable homodimers after interaction with the coactivators on a VDRE (DR+3). Of particular note, DR+4 and DR+5 hormone-response elements (HREs) may also support such interactions. Cotransfection experiments revealed further that the coactivators enhance ligand-induced VDR transcription on these elements. Our studies suggest the important role of VDR homodimers, in addition to VDR/RXR heterodimers, in vitamin D-induced transactivation. Thus, specific coactivator-VDR interactions on HREs may determine target gene transactivation.

MeSH terms

  • Cell Nucleus / metabolism*
  • Electrophoresis
  • Histone Acetyltransferases
  • Humans
  • Ligands
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 3
  • Plasmids / genetics
  • Receptors, Calcitriol / metabolism*
  • Receptors, Steroid / genetics
  • Repetitive Sequences, Nucleic Acid / genetics*
  • Response Elements / genetics*
  • Thyroid Hormones / physiology
  • Transcription Factors / genetics
  • Transfection / genetics


  • Ligands
  • Receptors, Calcitriol
  • Receptors, Steroid
  • Thyroid Hormones
  • Transcription Factors
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 3