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J. Biol. Chem., Vol. 279, Issue 32, 33114-33122, August 6, 2004

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Transcriptional Repressor DREAM Interacts with Thyroid Transcription Factor-1 and Regulates Thyroglobulin Gene Expression^*

Marcos Rivas¶, Britt Mellström¶, José R. Naranjo||, and Pilar Santisteban

From the Dpto. Biología Molecular y Celular, Centro Nacional de Biotecnología, CSIC 28049 Madrid, Spain and the Instituto de Investigaciones Biomédicas, CSIC 28029 Madrid, Spain

Tissue-specific gene expression depends on the interaction between tissue-specific and general transcription factors. DREAM is a Ca²⁺-dependent transcriptional repressor widely expressed in the brain where it participates in nociception through its control of prodynorphin gene expression. In the periphery, DREAM is highly expressed in the thyroid gland, the immune system, and the reproductive organs. Here, we show that DREAM interacts with thyroid-specific transcription factor TTF-1 and regulates the expression of the thyroglobulin (Tg) gene. The mechanism also involves binding of DREAM to the thyroglobulin promoter and blockage of TTF-1-mediated transactivation. The TSH/cAMP pathway and Ca²⁺ signaling regulate DREAM-mediated transcriptional repression of the thyroglobulin gene. Furthermore, chromatin immunoprecipitation experiments in FRTL-5 cells confirmed that Tg is a bona fide target gene for DREAM transrepression in thyroid follicular cells.

Received for publication, March 30, 2004 , and in revised form, May 18, 2004.

^* This work was supported by grants from Direccion General Investigacion Cientifica y Técnica, Comunidad Autónoma de Madrid, and Fondo Investigaciones Sanitarias Seguridad Social, and the Human Frontiers Science Program RGP0156/2001B. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Both authors contributed equally to this work.

^|| To whom correspondence should be addressed: Dpto. Biologéa Molecular y Celular, CNB-CSIC, Campus Cantoblanco, 28049 Madrid, Spain. Tel.: 34-91-5854682; Fax: 34-91-5854506; E-mail: naranjo{at}cnb.csic.es.

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