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, Cristina Luongo, Antonia Elefante, Raffaele Ambrosio, Salvatore Salzano, Mariastella Zannini, Roberto Nitsch, Roberto Di Lauro, Guido Rossi, Gianfranco Fenzi, Domenico Salvatore

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)10171-10182
Number of pages12
JournalMolecular and Cellular Biology
Volume25
Issue number22
DOIs
Publication statusPublished - Nov 2005

    Fingerprint

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Dentice, M., Luongo, C., Elefante, A., Ambrosio, R., Salzano, S., Zannini, M., Nitsch, R., Di Lauro, R., Rossi, G., Fenzi, G., & Salvatore, D. (2005). Pendrin is a novel in vivo downstream target gene of the TTF-1/Nkx-2.1 homeodomain transcription factor in differentiated thyroid cells. Molecular and Cellular Biology, 25(22), 10171-10182. https://doi.org/10.1128/MCB.25.22.10171-10182.2005