Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene

doi:10.1210/me.7.12.1589

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Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene

D Civitareale, MP Castelli, P Falasca and A Saiardi
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.

The TSH receptor (TSHr) is one of the most important thyroid differentiation markers. The binding of the TSH hormone to its receptor is an essential step in the modulation of thyroid function and differentiation. Here we report that the thyroid transcription factor 1 (TTF1), a transcription factor essential for thyroid-specific gene expression, binds to the TSHr minimal promoter. The promoter, when mutated at this binding site, shows a decreased activity in thyroid cells. In cotransfection experiments in nonthyroid cells, TTF1 is able to trans-activate the TSHr minimal promoter. This finding strengthens the importance of TTF1 in the maintenance of thyroid differentiation. The promoters of the main thyroid differentiation markers thyroglobulin, thyroperoxidase, and now TSHr, are regulated by TTF1.

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Endocrinology	Endocrine Reviews	J. Clin. End. & Metab.
Molecular Endocrinology	Recent Prog. Horm. Res.	All Endocrine Journals

				G Riesco-Eizaguirre, P Gutierrez-Martinez, M A Garcia-Cabezas, M Nistal, and P Santisteban The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I- targeting to the membrane. Endocr. Relat. Cancer, March 1, 2006; 13(1): 257 - 269. [Abstract] [Full Text] [PDF]

				R.-Y. Lin, A. Kubo, G. M. Keller, and T. F. Davies Committing Embryonic Stem Cells to Differentiate into Thyrocyte-Like Cells in Vitro Endocrinology, June 1, 2003; 144(6): 2644 - 2649. [Abstract] [Full Text] [PDF]

				K. Taki, T. Kogai, Y. Kanamoto, J. M. Hershman, and G. A. Brent A Thyroid-Specific Far-Upstream Enhancer in the Human Sodium/Iodide Symporter Gene Requires Pax-8 Binding and Cyclic Adenosine 3',5'-Monophosphate Response Element-Like Sequence Binding Proteins for Full Activity and Is Differentially Regulated in Normal and Thyroid Cancer Cells Mol. Endocrinol., October 1, 2002; 16(10): 2266 - 2282. [Abstract] [Full Text] [PDF]

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				C. Missero, M. T. Pirro, and R. Di Lauro Multiple Ras Downstream Pathways Mediate Functional Repression of the Homeobox Gene Product TTF-1 Mol. Cell. Biol., April 15, 2000; 20(8): 2783 - 2793. [Abstract] [Full Text]

				F. Schuppert, D. Ehrenthal, A. Frilling, K. Suzuki, G. Napolitano, and L. D. Kohn Increased Major Histocompatibility Complex (MHC) Expression in Nontoxic Goiters Is Associated with Iodide Depletion, Enhanced Ability of the Follicular Thyroglobulin to Increase MHC Gene Expression, and Thyroid Autoantibodies J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 858 - 867. [Abstract] [Full Text]

				R. S. Brown, V. Shalhoub, S. Coulter, S. Alex, I. Joris, W. De Vito, J. Lian, and G. S. Stein Developmental Regulation of Thyrotropin Receptor Gene Expression in the Fetal and Neonatal Rat Thyroid: Relation to Thyroid Morphology and to Thyroid-Specific Gene Expression Endocrinology, January 1, 2000; 141(1): 340 - 345. [Abstract] [Full Text] [PDF]

				M. Ohmori, N. Harii, T. Endo, and T. Onaya Tumor Necrosis Factor-{alpha} Regulation of Thyroid Transcription Factor-1 and Pax-8 in Rat Thyroid FRTL-5 Cells Endocrinology, October 1, 1999; 140(10): 4651 - 4658. [Abstract] [Full Text]

				K. Suzuki, S. Lavaroni, A. Mori, F. Okajima, S. Kimura, R. Katoh, A. Kawaoi, and L. D. Kohn Thyroid Transcription Factor 1�Is Calcium Modulated and Coordinately Regulates Genes Involved in Calcium Homeostasis in C Cells Mol. Cell. Biol., December 1, 1998; 18(12): 7410 - 7422. [Abstract] [Full Text]

				H. Shimura, A. Miyazaki, K. Haraguchi, T. Endo, and T. Onaya Analysis of Differentiation-Induced Expression Mechanisms of Thyrotropin Receptor Gene in Adipocytes Mol. Endocrinol., October 1, 1998; 12(10): 1473 - 1486. [Abstract] [Full Text]

				K. Suzuki, S. Lavaroni, A. Mori, M. Ohta, J. Saito, M. Pietrarelli, D. S. Singer, S. Kimura, R. Katoh, A. Kawaoi, et al. Autoregulation of thyroid-specific gene transcription by thyroglobulin PNAS, July 7, 1998; 95(14): 8251 - 8256. [Abstract] [Full Text] [PDF]

				J. A. Velasco, A. Acebron, M. Zannini, J. MartIn-Perez, R. Di Lauro, and P. Santisteban Ha-ras Interference with Thyroid Cell Differentiation Is Associated with a Down-Regulation of Thyroid Transcription Factor-1 Phosphorylation Endocrinology, June 1, 1998; 139(6): 2796 - 2802. [Abstract] [Full Text] [PDF]

				K. Devriendt, C. Vanhole, G. Matthijs, and F. de Zegher Deletion of Thyroid Transcription Factor-1 Gene in an Infant with Neonatal Thyroid Dysfunction and Respiratory Failure N. Engl. J. Med., April 30, 1998; 338(18): 1317 - 1318. [Full Text]

ARTICLES

Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene

				H. Oguchi and S. Kimura Multiple Transcripts Encoded by the Thyroid-Specific Enhancer-Binding Protein (T/EBP)/Thyroid-Specific Transcription Factor-1 (TTF-1) Gene: Evidence of Autoregulation Endocrinology, April 1, 1998; 139(4): 1999 - 2006. [Abstract] [Full Text] [PDF]

				T. Endo, M. Kaneshige, M. Nakazato, M. Ohmori, N. Harii, and T. Onaya Thyroid Transcription Factor-1 Activates the Promoter Activity of Rat Thyroid Na+/I- Symporter Gene Mol. Endocrinol., October 1, 1997; 11(11): 1747 - 1755. [Abstract] [Full Text]

				M. Saji, M. Shong, G. Napolitano, L. A. Palmer, S.-I. Taniguchi, M. Ohmori, M. Ohta, K. Suzuki, S. L. Kirshner, C. Giuliani, et al. Regulation of Major Histocompatibility Complex Class I Gene Expression in Thyroid Cells. ROLE OF THE cAMP RESPONSE ELEMENT-LIKE SEQUENCE J. Biol. Chem., August 8, 1997; 272(32): 20096 - 20107. [Abstract] [Full Text] [PDF]

				T. Saito, T. Endo, M. Nakazato, T. Kogai, and T. Onaya Thyroid-Stimulating Hormone-Induced Down-Regulation of Thyroid Transcription Factor 1 in Rat Thyroid FRTL-5 Cells Endocrinology, February 1, 1997; 138(2): 602 - 606. [Abstract] [Full Text] [PDF]

				S Kimura, Y Hara, T Pineau, P Fernandez-Salguero, C H Fox, J M Ward, and F J Gonzalez The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. Genes & Dev., January 1, 1996; 10(1): 60 - 69. [Abstract] [PDF]

				D�v. L. Rossi, A. Acebr�n, and P. Santisteban Function of the Homeo and Paired Domain Proteins TTF-1 and Pax-8 in Thyroid Cell Proliferation J. Biol. Chem., September 29, 1995; 270(39): 23139 - 23142. [Abstract] [Full Text] [PDF]

				C. Missero, M. T. Pirro, S. Simeone, M. Pischetola, and R. Di Lauro The DNA Glycosylase T:G Mismatch-specific Thymine DNA Glycosylase Represses Thyroid Transcription Factor-1-activated Transcription J. Biol. Chem., August 31, 2001; 276(36): 33569 - 33575. [Abstract] [Full Text] [PDF]