We have examined vitamin D receptor (VDR), thyroid hormone receptor (TR), and retinoid X receptor (RXR) 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 (T)-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 T-mediated transcription which may be significant in tissues where VDR and TR are co-expressed.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				Y. Liu, S. Ando, X. Xia, R. Yao, M. Kim, J. Fondell, and P. M. Yen p62, A TFIIH Subunit, Directly Interacts with Thyroid Hormone Receptor and Enhances T3-Mediated Transcription Mol. Endocrinol., April 1, 2005; 19(4): 879 - 884. [Abstract] [Full Text] [PDF]

				J.-N. Bastie, N. Balitrand, F. Guidez, I. Guillemot, J. Larghero, C. Calabresse, C. Chomienne, and L. Delva 1{alpha},25-Dihydroxyvitamin D3 Transrepresses Retinoic Acid Transcriptional Activity via Vitamin D Receptor in Myeloid Cells Mol. Endocrinol., November 1, 2004; 18(11): 2685 - 2699. [Abstract] [Full Text] [PDF]

				J.-C. Hsieh, J. M. Sisk, P. W. Jurutka, C. A. Haussler, S. A. Slater, M. R. Haussler, and C. C. Thompson Physical and Functional Interaction between the Vitamin D Receptor and Hairless Corepressor, Two Proteins Required for Hair Cycling J. Biol. Chem., October 3, 2003; 278(40): 38665 - 38674. [Abstract] [Full Text] [PDF]

				E. Ingley, D. Chappell, S. Y. K. Poon, M. K. Sarna, J. G. Beaumont, J. H. Williams, J. P. Stillitano, S. Tsai, P. J. Leedman, P. A. Tilbrook, et al. Thyroid Hormone Receptor-interacting Protein 1 Modulates Cytokine and Nuclear Hormone Signaling in Erythroid Cells J. Biol. Chem., November 9, 2001; 276(46): 43428 - 43434. [Abstract] [Full Text] [PDF]

				P. M. Yen Physiological and Molecular Basis of Thyroid Hormone Action Physiol Rev, July 1, 2001; 81(3): 1097 - 1142. [Abstract] [Full Text] [PDF]

				M Li, H Chiba, X Warot, N Messaddeq, C Gerard, P Chambon, and D Metzger RXR-alpha ablation in skin keratinocytes results in alopecia and epidermal alterations Development, January 3, 2001; 128(5): 675 - 688. [Abstract] [PDF]

				Y. Sakai and M. B. Demay Evaluation of Keratinocyte Proliferation and Differentiation in Vitamin D Receptor Knockout Mice Endocrinology, June 1, 2000; 141(6): 2043 - 2049. [Abstract] [Full Text] [PDF]

				A. M. Jiménez-Lara and A. Aranda Vitamin D Represses Retinoic Acid-Dependent Transactivation of the Retinoic Acid Receptor-{beta}2 Promoter: The AF-2 Domain of the Vitamin D Receptor Is Required for Transrepression Endocrinology, June 1, 1999; 140(6): 2898 - 2907. [Abstract] [Full Text]

				N. Koibuchi, Y. Liu, H. Fukuda, A. Takeshita, P. M. Yen, and W. W. Chin ROR{alpha} Augments Thyroid Hormone Receptor-Mediated Transcriptional Activation Endocrinology, March 1, 1999; 140(3): 1356 - 1364. [Abstract] [Full Text]

				M. Raval-Pandya, L. P. Freedman, H. Li, and S. Christakos Thyroid Hormone Receptor Does Not Heterodimerize with the Vitamin D Receptor but Represses Vitamin D Receptor-Mediated Transactivation Mol. Endocrinol., September 1, 1998; 12(9): 1367 - 1379. [Abstract] [Full Text]

				A. Takeshita, P. M. Yen, M. Ikeda, G. R. Cardona, Y. Liu, N. Koibuchi, E. R. Norwitz, and W. W. Chin Thyroid Hormone Response Elements Differentially Modulate the Interactions of Thyroid Hormone Receptors with Two Receptor Binding Domains in the Steroid Receptor Coactivator-1 J. Biol. Chem., August 21, 1998; 273(34): 21554 - 21562. [Abstract] [Full Text] [PDF]

				G. W. Anderson, R. J. Larson, D. R. Oas, C. R. Sandhofer, H. L. Schwartz, C. N. Mariash, and J. H. Oppenheimer Chicken Ovalbumin Upstream Promoter-Transcription Factor (COUP-TF) Modulates Expression of the Purkinje Cell Protein-2 Gene. A POTENTIAL ROLE FOR COUP-TF IN REPRESSING PREMATURE THYROID HORMONE ACTION IN THE DEVELOPING BRAIN J. Biol. Chem., June 26, 1998; 273(26): 16391 - 16399. [Abstract] [Full Text] [PDF]

				H. Li, C. Leo, D. J. Schroen, and J. D. Chen Characterization of Receptor Interaction and Transcriptional Repression by the Corepressor SMRT Mol. Endocrinol., December 1, 1997; 11(13): 2025 - 2037. [Abstract] [Full Text] [PDF]

				Y. Ezura, O. Tournay, A. Nifuji, and M. Noda Identification of a Novel Suppressive Vitamin D Response Sequence in the 5'-Flanking Region of the Murine Id1 Gene J. Biol. Chem., November 21, 1997; 272(47): 29865 - 29872. [Abstract] [Full Text] [PDF]

				A. Takeshita, G. R. Cardona, N. Koibuchi, C.-S. Suen, and W. W. Chin TRAM-1, A Novel 160-kDa Thyroid Hormone Receptor Activator Molecule, Exhibits Distinct Properties from Steroid Receptor Coactivator-1 J. Biol. Chem., October 31, 1997; 272(44): 27629 - 27634. [Abstract] [Full Text] [PDF]

				A. Sugawara, N. Sanno, N. Takahashi, R. Y. Osamura, and K. Abe Retinoid X Receptors in the Kidney: Their Protein Expression and Functional Significance Endocrinology, August 1, 1997; 138(8): 3175 - 3180. [Abstract] [Full Text] [PDF]

				P. M. Yen, Y. Liu, J. J. Palvimo, M. Trifiro, J. Whang, L. Pinsky, O. A. Jänne, and W. W. Chin Mutant and Wild-Type Androgen Receptors Exhibit Cross-Talk on Androgen-, Glucocorticoid-, and Progesterone-Mediated Transcription Mol. Endocrinol., February 1, 1997; 11(2): 162 - 171. [Abstract] [Full Text]

				H. Masuyama, S. C. Jefcoat Jr., and P. N. MacDonald The N-Terminal Domain of Transcription Factor IIB Is Required for Direct Interaction with the Vitamin D Receptor and Participates in Vitamin D-Mediated Transcription Mol. Endocrinol., February 1, 1997; 11(2): 218 - 228. [Abstract] [Full Text]