PMID- 10698207 OWN - NLM STAT- MEDLINE DCOM- 20000316 LR - 20091119 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 141 IP - 3 DP - 2000 Mar TI - Nuclear receptor coactivators facilitate vitamin D receptor homodimer action on direct repeat hormone response elements. PG - 1281-4 AB - 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. FAU - Takeshita, A AU - Takeshita A AD - Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. akira18@mail7.dddd.ne.jp FAU - Ozawa, Y AU - Ozawa Y FAU - Chin, W W AU - Chin WW LA - eng PT - Journal Article PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Ligands) RN - 0 (Receptors, Calcitriol) RN - 0 (Receptors, Steroid) RN - 0 (Thyroid Hormones) RN - 0 (Transcription Factors) RN - EC 2.3.1.48 (Histone Acetyltransferases) RN - EC 2.3.1.48 (NCOA1 protein, human) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 3) SB - IM MH - Cell Nucleus/*metabolism MH - Electrophoresis MH - Histone Acetyltransferases MH - Humans MH - Ligands MH - Nuclear Receptor Coactivator 1 MH - Nuclear Receptor Coactivator 3 MH - Plasmids/genetics MH - Receptors, Calcitriol/*metabolism MH - Receptors, Steroid/genetics MH - Repetitive Sequences, Nucleic Acid/*genetics MH - Response Elements/*genetics MH - Thyroid Hormones/physiology MH - Transcription Factors/genetics MH - Transfection/genetics EDAT- 2000/03/04 09:00 MHDA- 2000/03/18 09:00 CRDT- 2000/03/04 09:00 PHST- 2000/03/04 09:00 [pubmed] PHST- 2000/03/18 09:00 [medline] PHST- 2000/03/04 09:00 [entrez] AID - 10.1210/endo.141.3.7441 [doi] PST - ppublish SO - Endocrinology. 2000 Mar;141(3):1281-4. doi: 10.1210/endo.141.3.7441.