Human Thyroid Oxidases genes promoter activity in thyrocytes does not appear to be functionally dependent on Thyroid Transcription Factor-1 or Pax8.
Thyroid Oxidases (ThOX/DUOX) genes encode proteins that are thought to play a crucial role in the biosynthesis of thyroid hormone by providing the oxidizing agent required to allow the organification of iodine. The expression of these genes is not restricted to the thyroid, but the corresponding mRNAs are found in the thyrocyte more abundantly than in several other cell types. It raises the question whether the same transcription factors, namely Thyroid Transcription Factor-1 (TTF-1) and Pax8, that control the expression of other genes involved in the differentiated thyroid function, also regulate ThOX/DUOX gene transcription in the thyrocyte. We set up a functional co-transfection assay in which fusion proteins composed of the DNA-binding domain of either TTF-1 or Pax8 fused to the repressive domain of the drosophila engrailed protein were used to competitively counteract the activity of endogenous TTF-1 or Pax8 factor in the differentiated thyroid cell line PCCl3. Contrary to the Thyroglobulin or Thyroid Peroxidase promoter, the known regulatory elements of the human ThOX/DUOX genes displayed no reduction in transcriptional activity when either TTF-1 or Pax8 competitor was produced in the cell, indicating that the presently characterized control elements of human ThOX/DUOX genes are not responsive to these thyroid-specific transcription factors.
Christophe-Hobertus
Christiane
C
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles, IBMM, rue des Pr Jeener et Brachet, 12, B-6041 Charleroi (Gosselies), Belgium.
Christophe
Daniel
D
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007453:Iodide Peroxidase / Q000096:biosynthesis* / Q000235:genetics; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000235:genetics; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology; D013961:Thyroid Gland / Q000166:cytology / Q000201:enzymology*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000502:physiology
D004268:DNA-Binding Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; C504003:TTF1 protein, human; D014157:Transcription Factors; D007453:Iodide Peroxidase; D019255:NADPH Oxidases