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The Synergistic Activity of Thyroid Transcription Factor 1 and Pax 8 Relies on the Promoter/Enhancer Interplay

Laboratory of Immunology (S.M., R.D.L., P.G.N., D.C.), Regina Elena Cancer Institute, Rome 00158, Italy; Department of Pediatrics (R.D.L., E.Z.), Meyer Hospital, University of Florence, Florence 50132, Italy; and Institute of Neurobiology and Molecular Medicine (D.C.), Consiglio Nazionale delle Ricerche, Rome 00137, Italy

Address all correspondence and requests for reprints to: Dr. Donato Civitareale, Laboratory of Immunology, Regina Elena Cancer Institute, Via delle Messi d’Oro 156, Rome, Italy 00158. E-mail: dciv{at}yahoo.com.

The transcription factors, thyroid transcription factor 1 (TTF-1) and Pax 8, play a pivotal role in the transcriptional regulation of the thyroid differentiation marker genes and in the differentiation of the thyroid follicular cells. They have a very restricted tissue distribution, and the thyrocyte is the only cell type with the simultaneous expression of these factors. Here we show that TTF-1 and Pax 8 cooperatively activate their target genes and that their synergistic activity requires the cross-talk between enhancer and gene promoter. We have characterized the cis and trans requirements of the TTF1/Pax 8 synergistic activity on the thyroperoxidase gene. We show that their synergy is also important for thyroglobulin gene transcription.

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