Nuclear receptor coactivators facilitate vitamin D receptor homodimer action on direct repeat hormone response elements.
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.
Takeshita
A
A
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. akira18@mail7.dddd.ne.jp
Ozawa
Y
Y
Chin
W W
WW
D002467:Cell Nucleus / Q000378:metabolism*; D004586:Electrophoresis; D051548:Histone Acetyltransferases; D006801:Humans; D008024:Ligands; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D010957:Plasmids / Q000235:genetics; D018167:Receptors, Calcitriol / Q000378:metabolism*; D011987:Receptors, Steroid / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D020218:Response Elements / Q000235:genetics*; D013963:Thyroid Hormones / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection / Q000235:genetics
D008024:Ligands; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D013963:Thyroid Hormones; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3