Vitamin D receptors repress basal transcription and exert dominant negative activity on triiodothyronine-mediated transcriptional activity

Paul M. Yen, Ying Liu, Akira Sugawara, William W. Chin

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

We have examined vitamin D receptor (VDR), thyroid hormone receptor (TR), and retinoid X receptor β (RXRβ) binding to vitamin D response elements (VDREs), two thyroid hormone response elements (TREs) (DR4 and F2), and a retinoic acid response element (DR5). VDR/RXR bound well to the VDREs and to DR4 and DR5 using the electrophoretic mobility shift assay. Surprisingly, VDR/RXR also bound well to F2, which contains half-sites arranged as an inverted palindrome. In co-transfection experiments using CV-1 cells, we observed that VDR repressed basal transcription in the absence of ligand on DR3 and osteopontin VDREs and F2, but had no effect on DR4 or DR5. VDR selectively mediated ligand-dependent transcription on only VDREs. VDR also exhibited dominant negative activity as it blocked triiodothyronine (T3)- mediated transcriptional activity on DR4 and F2. These results demonstrate that VDR/RXR heterodimers can bind promiscuously to a wide range of hormone response elements, including inverted palindromes. Moreover, they show that unliganded VDRs, similar to TRs and retinoic acid receptors, can repress basal transcription. Last, they also suggest a novel repressor function of VDR on T3-mediated transcription which may be significant in tissues where VDR and TR are co-expressed.

Original languageEnglish
Pages (from-to)10910-10916
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number18
DOIs
Publication statusPublished - 1996 May 20

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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