HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 6, 3929-3936, February 9, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/6/3929    most recent M006743200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wu, Y. Articles by Koenig, R. J. Search for Related Content PubMed PubMed Citation Articles by Wu, Y. Articles by Koenig, R. J.

Thyroid Hormone Response Element Sequence and the Recruitment of Retinoid X Receptors for Thyroid Hormone Responsiveness^*

Yifei Wu, Bin Xu, and Ronald J. Koenig

From the Division of Endocrinology and Metabolism, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0678

Thyroid hormone receptors (TRs) are transcription factors that bind to thyroid hormone response elements (TREs) in the regulatory regions of target genes. TRs are thought to activate transcription primarily as heterodimers with retinoid X receptors (RXRs), with RXR binding upstream to the two directly repeated half-sites in a typical TRE. However, given that TRs and RXRs prefer to bind to different DNA sequences (T(A/G)AGGTCA and GGGGTCA), we postulate that only certain TREs require RXR-TR heterodimerization, depending on the TRE sequence. We have tested this hypothesis by comparing in Saccharomyces cerevisiae the functional activity of TR ± RXR on 10 naturally occurring mammalian TREs. S. cerevisiae was used as a model system because yeast lack endogenous nuclear receptors and thus can be manipulated to express TRs and/or RXRs. We first studied ligand-independent reporter gene activation, which reflects the activity of the activator function 1 (AF-1) domain. The 10 TREs formed a continuous spectrum from being fully dependent on RXR for TR AF-1 activity to being essentially independent of RXR. Relative independence of RXR generally was seen when the TRE upstream half-site has a TA or TG 5' to the core hexamer. Gel mobility shift assays revealed that functional independence of RXR correlates with the strong binding of TR alone, whereas more RXR dependence correlates with higher binding of RXR-TR heterodimers. Restoration of ligand-dependent (AF-2 domain) reporter gene activation was achieved by expression of the coactivator TIF2. This ligand-induced stimulation was stronger in the presence of TR alone than with RXR plus TR, suggesting a preference for TIF2 activation of TR homodimers. Overall the data support the notion that the TRE sequence plays an important role in determining the nuclear hormone receptor and coactivator requirements for TR action.

This article has been cited by other articles:

				P.-J. Tai, Y.-H. Huang, C.-H. Shih, R.-N. Chen, C.-D. Chen, W.-J. Chen, C.-S. Wang, and K.-H. Lin Direct Regulation of Androgen Receptor-Associated Protein 70 by Thyroid Hormone and Its Receptors Endocrinology, July 1, 2007; 148(7): 3485 - 3495. [Abstract] [Full Text] [PDF]

				L. F. R. Velasco, M. Togashi, P. G. Walfish, R. P. Pessanha, F. N. Moura, G. B. Barra, P. Nguyen, R. Rebong, C. Yuan, L. A. Simeoni, et al. Thyroid Hormone Response Element Organization Dictates the Composition of Active Receptor J. Biol. Chem., April 27, 2007; 282(17): 12458 - 12466. [Abstract] [Full Text] [PDF]

				C. B. Harvey, J. H. D. Bassett, P. Maruvada, P. M. Yen, and G. R. Williams The Rat Thyroid Hormone Receptor (TR) {Delta}{beta}3 Displays Cell-, TR Isoform-, and Thyroid Hormone Response Element-Specific Actions Endocrinology, April 1, 2007; 148(4): 1764 - 1773. [Abstract] [Full Text] [PDF]

				Y.-H. Huang, C.-Y. Lee, P.-J. Tai, C.-C. Yen, C.-Y. Liao, W.-J. Chen, C.-J. Liao, W.-L. Cheng, R.-N. Chen, S.-M. Wu, et al. Indirect Regulation of Human Dehydroepiandrosterone Sulfotransferase Family 1A Member 2 by Thyroid Hormones Endocrinology, May 1, 2006; 147(5): 2481 - 2489. [Abstract] [Full Text] [PDF]

				A. Kenessey and K. Ojamaa Ligand-mediated decrease of thyroid hormone receptor-{alpha}1 in cardiomyocytes by proteosome-dependent degradation and altered mRNA stability Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H813 - H821. [Abstract] [Full Text] [PDF]

				B. Xu and R. J. Koenig An RNA-binding Domain in the Thyroid Hormone Receptor Enhances Transcriptional Activation J. Biol. Chem., August 6, 2004; 279(32): 33051 - 33056. [Abstract] [Full Text] [PDF]

				M. S. Malo, W. Zhang, F. Alkhoury, P. Pushpakaran, M. A. Abedrapo, M. Mozumder, E. Fleming, A. Siddique, J. W. Henderson, and R. A. Hodin Thyroid Hormone Positively Regulates the Enterocyte Differentiation Marker Intestinal Alkaline Phosphatase Gene via an Atypical Response Element Mol. Endocrinol., August 1, 2004; 18(8): 1941 - 1962. [Abstract] [Full Text] [PDF]