This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dentice, M. Articles by Salvatore, D. Search for Related Content PubMed PubMed Citation Articles by Dentice, M. Articles by Salvatore, D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2005, p. 10171-10182, Vol. 25, No. 22
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.22.10171-10182.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Pendrin Is a Novel In Vivo Downstream Target Gene of the TTF-1/Nkx-2.1 Homeodomain Transcription Factor in Differentiated Thyroid Cells

Monica Dentice,^1, Cristina Luongo,^2, Antonia Elefante,² Raffaele Ambrosio,² Salvatore Salzano,³ Mariastella Zannini,^1,3 Roberto Nitsch,^1,3 Roberto Di Lauro,¹ Guido Rossi,¹ Gianfranco Fenzi,² and Domenico Salvatore^2*

Dipartimento di Biologia e Patologia Cellulare e Molecolare,¹ Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Università di Napoli "Federico II," 80131 Naples, Italy,² Istituto di Endocrinologia ed Oncologia Sperimentale, CNR-IEOS, 80131 Naples, Italy³

Received 6 August 2005/ Accepted 28 August 2005

Thyroid transcription factor gene 1 (TTF-1) is a homeobox-containing gene involved in thyroid organogenesis. During early thyroid development, the homeobox gene Nkx-2.5 is expressed in thyroid precursor cells coincident with the appearance of TTF-1. The aim of this study was to investigate the molecular mechanisms underlying thyroid-specific gene expression. We show that the Nkx-2.5 C terminus interacts with the TTF-1 homeodomain and, moreover, that the expression of a dominant-negative Nkx-2.5 isoform (N188K) in thyroid cells reduces TTF-1-driven transcription by titrating TTF-1 away from its target DNA. This process reduced the expression of several thyroid-specific genes, including pendrin and thyroglobulin. Similarly, down-regulation of TTF-1 by RNA interference reduced the expression of both genes, whose promoters are sensitive to and directly associate with TTF-1 in the chromatin context. In conclusion, we demonstrate that pendrin and thyroglobulin are downstream targets in vivo of TTF-1, whose action is a prime factor in controlling thyroid differentiation in vivo.

---

* Corresponding author. Mailing address: Department of Endocrinology and Molecular and Clinical Oncology, University of Naples "Federico II," Via S. Pansini 5, 80131 Naples, Italy. Phone: (39) 081 7463780. Fax: (39) 081 7463668. E-mail: domsalva{at}unina.it.

Supplemental material for this article may be found at http://mcb.asm.org/.

M.D. and C.L. contributed equally to this work.

---

Molecular and Cellular Biology, November 2005, p. 10171-10182, Vol. 25, No. 22
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.22.10171-10182.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Carre, A., Szinnai, G., Castanet, M., Sura-Trueba, S., Tron, E., Broutin-L'Hermite, I., Barat, P., Goizet, C., Lacombe, D., Moutard, M.-L., Raybaud, C., Raynaud-Ravni, C., Romana, S., Ythier, H., Leger, J., Polak, M. (2009). Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case. Hum Mol Genet 18: 2266-2276 [Abstract] [Full Text]  
• Adler, L., Efrati, E., Zelikovic, I. (2008). Molecular mechanisms of epithelial cell-specific expression and regulation of the human anion exchanger (pendrin) gene. Am. J. Physiol. Cell Physiol. 294: C1261-C1276 [Abstract] [Full Text]  
• Szinnai, G., Lacroix, L., Carre, A., Guimiot, F., Talbot, M., Martinovic, J., Delezoide, A.-L., Vekemans, M., Michiels, S., Caillou, B., Schlumberger, M., Bidart, J.-M., Polak, M. (2007). Sodium/Iodide Symporter (NIS) Gene Expression Is the Limiting Step for the Onset of Thyroid Function in the Human Fetus. J. Clin. Endocrinol. Metab. 92: 70-76 [Abstract] [Full Text]  
• Dentice, M., Cordeddu, V., Rosica, A., Ferrara, A. M., Santarpia, L., Salvatore, D., Chiovato, L., Perri, A., Moschini, L., Fazzini, C., Olivieri, A., Costa, P., Stoppioni, V., Baserga, M., De Felice, M., Sorcini, M., Fenzi, G., Di Lauro, R., Tartaglia, M., Macchia, P. E. (2006). Missense Mutation in the Transcription Factor NKX2-5: A Novel Molecular Event in the Pathogenesis of Thyroid Dysgenesis. J. Clin. Endocrinol. Metab. 91: 1428-1433 [Abstract] [Full Text]