The synergistic activity of thyroid transcription factor 1 and Pax 8 relies on the promoter/enhancer interplay.
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.
Miccadei
Stefania
S
Laboratory of Immunology, Regina Elena Cancer Institute, Rome 00158, Italy.
De Leo
Rossana
R
Zammarchi
Enrico
E
Natali
Pier Giorgio
PG
Civitareale
Donato
D
D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D006367:HeLa Cells; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D010957:Plasmids; D011401:Promoter Regions, Genetic; D013954:Thyroglobulin / Q000235:genetics; D013961:Thyroid Gland / Q000254:growth & development*; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D013954:Thyroglobulin; D007453:Iodide Peroxidase