Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene.
The TSH receptor (TSHr) is one of the most important thyroid differentiation markers. The binding of the TSH hormone to its receptor is an essential step in the modulation of thyroid function and differentiation. Here we report that the thyroid transcription factor 1 (TTF1), a transcription factor essential for thyroid-specific gene expression, binds to the TSHr minimal promoter. The promoter, when mutated at this binding site, shows a decreased activity in thyroid cells. In cotransfection experiments in nonthyroid cells, TTF1 is able to trans-activate the TSHr minimal promoter. This finding strengthens the importance of TTF1 in the maintenance of thyroid differentiation. The promoters of the main thyroid differentiation markers thyroglobulin, thyroperoxidase, and now TSHr, are regulated by TTF1.
Civitareale
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Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.
Castelli
M P
MP
Falasca
P
P
Saiardi
A
A
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding; D051381:Rats; D011989:Receptors, Thyrotropin / Q000096:biosynthesis / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D015533:Transcriptional Activation
C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D011989:Receptors, Thyrotropin; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors