scholarly journals Two thyroid hormone response elements are present in the promoter of human thyroid hormone receptor beta 1.

1994 ◽  
Vol 8 (3) ◽  
pp. 305-314 ◽  
Author(s):  
S Suzuki ◽  
T Miyamoto ◽  
A Opsahl ◽  
A Sakurai ◽  
L J DeGroot
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Human Thyroid ◽  
Hormone Response ◽  
Response Elements ◽  
Hormone Response Elements ◽  
Receptor Beta

scholarly journals Ligand-dependent and -independent transactivation by thyroid hormone receptor beta 2 is determined by the structure of the hormone response element.

1995 ◽  
Vol 15 (9) ◽  
pp. 4718-4726 ◽  
Author(s):  
M Sjöberg ◽  
B Vennström
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hormone Response ◽  
Response Element ◽  
Response Elements ◽  
Hormone Response Elements ◽  
Hormone Response Element ◽  
Beta 2 ◽  
Receptor Beta

Chicken thyroid hormone receptor beta 2 (cTR beta 2) is likely to serve specific functions in gene regulation since it possesses a unique N-terminal domain and is expressed in very few tissues. We demonstrate here that TR beta 2 exhibits distinct transactivation properties which are dependent on the availability of ligand and on the structure of the hormone response element. First, a strong ligand-independent transactivation was observed with hormone response elements composed of direct repeats and everted repeats. Second, TR beta 2 was induced by triiodothyronine to transactivate more efficiently than TR beta 0 on palindromic and everted-repeat types of hormone response elements. However, coexpression of the retinoid X receptor reduced the strong transactivation by TR beta 2 but not by TR beta 0 via palindromic response elements, suggesting that TR beta 2 can transactivate as a homodimer. Finally, the N terminus of TR beta 2 contains two distinct transactivation regions rich in tyrosines, which are essential for transactivation. Our results thus show that the activity of the novel transactivating region of TR beta 2 is dependent on the organization of the half-sites in the response element.

scholarly journals Identification of thyroid hormone response elements in vivo using mice expressing a tagged thyroid hormone receptor α1

2013 ◽  
Vol 33 (2) ◽  
Author(s):  
Susi Dudazy-Gralla ◽  
Kristina Nordström ◽  
Peter Josef Hofmann ◽  
Dina Abdul Meseh ◽  
Lutz Schomburg ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Nuclear Receptor ◽  
Hormone Receptor ◽  
Target Genes ◽  
Thyroid Hormone Receptor ◽  
Hormone Response ◽  
Protein Fusion ◽  
Response Elements ◽  
Hormone Response Elements

TRα1 (thyroid hormone receptor α1) is well recognized for its importance in brain development. However, due to the difficulties in predicting TREs (thyroid hormone response elements) in silico and the lack of suitable antibodies against TRα1 for ChIP (chromatin immunoprecipitation), only a few direct TRα1 target genes have been identified in the brain. Here we demonstrate that mice expressing a TRα1–GFP (green fluorescent protein) fusion protein from the endogenous TRα locus provide a valuable animal model to identify TRα1 target genes. To this end, we analysed DNA–TRα1 interactions in vivo using ChIP with an anti-GFP antibody. We validated our system using established TREs from neurogranin and hairless, and by verifying additional TREs from known TRα1 target genes in brain and heart. Moreover, our model system enabled the identification of novel TRα1 target genes such as RNF166 (ring finger protein 166). Our results demonstrate that transgenic mice expressing a tagged nuclear receptor constitute a feasible approach to study receptor–DNA interactions in vivo, circumventing the need for specific antibodies. Models like the TRα1–GFP mice may thus pave the way for genome-wide mapping of nuclear receptor-binding sites, and advance the identification of novel target genes in vivo.

scholarly journals Thyroid hormone regulation of prohormone convertase 1 (PC1): regional expression in rat brain and in vitro characterization of negative thyroid hormone response elements

2004 ◽  
Vol 33 (1) ◽  
pp. 21-33 ◽  
Author(s):  
X Shen ◽  
QL Li ◽  
GA Brent ◽  
TC Friedman
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Specific Binding ◽  
Gh3 Cells ◽  
Mrna Levels ◽  
Hormone Response ◽  
Mobility Shift ◽  
Response Elements ◽  
Hormone Response Elements

Most pro-neuropeptides are processed by the prohormone convertases, PC1 and PC2. We previously reported that changes in thyroid status altered anterior pituitary PC1 mRNA and this regulation was due to triiodothyronine (T(3))-dependent interaction of thyroid hormone receptor (TR) with negative thyroid hormone response elements (nTREs) contained in a large region of the human PC1 promoter. In this study, we demonstrated that hypothyroidism stimulated, while hyperthyroidism suppressed, PC1 mRNA levels in rat hypothalamus and cerebral cortex, but not in hippocampus. In situ hybridization was used to confirm real-time PCR changes and localize the regulation within the hypothalamus and cortex. Using a human PC1 (hPC1) promoter construct (with and without deletions in two regions that each contain a negative TRE) transiently transfected into GH3 cells, we found that T(3) negatively regulated hPC1 promoter activity, and this regulation required both of these two regions. Electrophoretic mobility shift assays (EMSAs) using purified thyroid hormone receptor alpha1 (TRalpha1) and retinoid X receptor beta (RXRbeta) proteins demonstrated that RXR and TRalpha both bound the PC1 promoter. Addition of TRalpha1/RXRbeta to the wild-type PC1 probe demonstrated binding as both homodimers and a heterodimer. EMSAs with oligonucleotides containing deletion mutations of the putative nTREs demonstrated that the proximal nTRE binds more strongly to TR and RXR than the distal nTRE, but that both regions exhibit specific binding. We conclude that there are multiple novel TRE-like sequences in the hPC1 promoter and that these regions act in a unique manner to facilitate the negative effect of thyroid hormone on PC1.

scholarly journals Determination of Nuclear Receptor Corepressor Interactions with the Thyroid Hormone Receptor

2003 ◽  
Vol 17 (2) ◽  
pp. 273-286 ◽  
Author(s):  
Anita Makowski ◽  
Sabrina Brzostek ◽  
Ronald N. Cohen ◽  
Anthony N. Hollenberg
Keyword(s):  
Thyroid Hormone ◽  
Nuclear Receptor ◽  
Hormone Receptor ◽  
Mammalian Cells ◽  
Thyroid Hormone Receptor ◽  
Hormone Response ◽  
Response Elements ◽  
Hormone Response Elements ◽  
Nuclear Receptor Corepressor ◽  
Repression Complex

Abstract The thyroid hormone receptor (TR) recruits the nuclear corepressors, nuclear receptor corepressor (NCoR) and silencing mediator of retinoid and thyroid hormone receptors (SMRT), to target DNA elements in the absence of ligand. While the TR preferentially recruits NCoR, the mechanism remains unclear. The corepressors interact with the TR via interacting domains (IDs) present in their C terminus which contain a conserved motif termed a CoRNR box. Despite their similarity, the corepressor IDs allow for nuclear receptor specificity. Here we demonstrate that NCoR stabilizes the TR homodimer when bound to DNA by preventing its dissociation from thyroid hormone response elements. This suggests that NCoR acts to hold the repression complex in place on target elements. The TR homodimer recruits NCoR through two of its three IDs, one of which is not present in SMRT. This unique ID, N3, contains a CoRNR box but lacks the extended helical motif present in each of the other IDs. Instead, N3 contains an isoleucine just proximal to this motif. This isoleucine is also conserved in N2 but not in the corresponding S2 domain in SMRT. On thyroid hormone response elements and in mammalian cells this residue is critical in both N3 and N2 for high-affinity TR binding. In addition, this residue also controls specificity for the interactions of TR with NCoR. Together these data suggest that the specific recruitment of NCoR by the TR through a unique motif allows for stabilization of the repression complex on target elements.

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