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. 1998 Apr 1;331(Pt 1):37–40. doi: 10.1042/bj3310037

PAX 8 activates the enhancer of the human thyroperoxidase gene.

C Esposito 1, S Miccadei 1, A Saiardi 1, D Civitareale 1
PMCID: PMC1219318  PMID: 9512459

Abstract

In this study we report on a novel natural target of the paired domain transcription factor PAX 8 in the enhancer element of the human thyroperoxidase gene, one of the most important thyroid differentiation markers. It is the primary enzyme involved in thyroid hormone synthesis and PAX 8 has been previously identified as an activating factor of the rat thyroperoxidase gene promoter. In vitro, PAX 8 binds a cis element of the human enhancer and its exogenous expression induces the enhancer activity in co-transfection experiments in Cos-7 cells. When mutated at this binding site, the enhancer is no longer activated by PAX 8. Our finding strengthens the PAX 8 role in the maintenance of thyroid differentiation and in particular in the tissue-specific thyroperoxidase gene expression.

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Selected References

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  1. Abramowicz M. J., Vassart G., Christophe D. Functional study of the human thyroid peroxidase gene promoter. Eur J Biochem. 1992 Feb 1;203(3):467–473. doi: 10.1111/j.1432-1033.1992.tb16571.x. [DOI] [PubMed] [Google Scholar]
  2. Civitareale D., Castelli M. P., Falasca P., Saiardi A. Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene. Mol Endocrinol. 1993 Dec;7(12):1589–1595. doi: 10.1210/mend.7.12.8145764. [DOI] [PubMed] [Google Scholar]
  3. Civitareale D., Lonigro R., Sinclair A. J., Di Lauro R. A thyroid-specific nuclear protein essential for tissue-specific expression of the thyroglobulin promoter. EMBO J. 1989 Sep;8(9):2537–2542. doi: 10.1002/j.1460-2075.1989.tb08391.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Czerny T., Busslinger M. DNA-binding and transactivation properties of Pax-6: three amino acids in the paired domain are responsible for the different sequence recognition of Pax-6 and BSAP (Pax-5). Mol Cell Biol. 1995 May;15(5):2858–2871. doi: 10.1128/mcb.15.5.2858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Czerny T., Schaffner G., Busslinger M. DNA sequence recognition by Pax proteins: bipartite structure of the paired domain and its binding site. Genes Dev. 1993 Oct;7(10):2048–2061. doi: 10.1101/gad.7.10.2048. [DOI] [PubMed] [Google Scholar]
  6. Damante G., Di Lauro R. Thyroid-specific gene expression. Biochim Biophys Acta. 1994 Aug 2;1218(3):255–266. doi: 10.1016/0167-4781(94)90176-7. [DOI] [PubMed] [Google Scholar]
  7. Dumont J. E., Lamy F., Roger P., Maenhaut C. Physiological and pathological regulation of thyroid cell proliferation and differentiation by thyrotropin and other factors. Physiol Rev. 1992 Jul;72(3):667–697. doi: 10.1152/physrev.1992.72.3.667. [DOI] [PubMed] [Google Scholar]
  8. Dörfler P., Busslinger M. C-terminal activating and inhibitory domains determine the transactivation potential of BSAP (Pax-5), Pax-2 and Pax-8. EMBO J. 1996 Apr 15;15(8):1971–1982. [PMC free article] [PubMed] [Google Scholar]
  9. Foti D., Gestautas J., Rapoport B. Studies on the functional activity of the promoter for the human thyroid peroxidase gene. Biochem Biophys Res Commun. 1990 Apr 16;168(1):281–287. doi: 10.1016/0006-291x(90)91705-w. [DOI] [PubMed] [Google Scholar]
  10. Francis-Lang H., Price M., Polycarpou-Schwarz M., Di Lauro R. Cell-type-specific expression of the rat thyroperoxidase promoter indicates common mechanisms for thyroid-specific gene expression. Mol Cell Biol. 1992 Feb;12(2):576–588. doi: 10.1128/mcb.12.2.576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gérard C. M., Lefort A., Christophe D., Libert F., Van Sande J., Dumont J. E., Vassart G. Control of thyroperoxidase and thyroglobulin transcription by cAMP: evidence for distinct regulatory mechanisms. Mol Endocrinol. 1989 Dec;3(12):2110–2118. doi: 10.1210/mend-3-12-2110. [DOI] [PubMed] [Google Scholar]
  12. Ho S. N., Hunt H. D., Horton R. M., Pullen J. K., Pease L. R. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene. 1989 Apr 15;77(1):51–59. doi: 10.1016/0378-1119(89)90358-2. [DOI] [PubMed] [Google Scholar]
  13. Hollon T., Yoshimura F. K. Variation in enzymatic transient gene expression assays. Anal Biochem. 1989 Nov 1;182(2):411–418. doi: 10.1016/0003-2697(89)90616-7. [DOI] [PubMed] [Google Scholar]
  14. Kikkawa F., Gonzalez F. J., Kimura S. Characterization of a thyroid-specific enhancer located 5.5 kilobase pairs upstream of the human thyroid peroxidase gene. Mol Cell Biol. 1990 Dec;10(12):6216–6224. doi: 10.1128/mcb.10.12.6216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mizuno K., Gonzalez F. J., Kimura S. Thyroid-specific enhancer-binding protein (T/EBP): cDNA cloning, functional characterization, and structural identity with thyroid transcription factor TTF-1. Mol Cell Biol. 1991 Oct;11(10):4927–4933. doi: 10.1128/mcb.11.10.4927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Noll M. Evolution and role of Pax genes. Curr Opin Genet Dev. 1993 Aug;3(4):595–605. doi: 10.1016/0959-437x(93)90095-7. [DOI] [PubMed] [Google Scholar]
  17. Plachov D., Chowdhury K., Walther C., Simon D., Guenet J. L., Gruss P. Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland. Development. 1990 Oct;110(2):643–651. doi: 10.1242/dev.110.2.643. [DOI] [PubMed] [Google Scholar]
  18. Saito T., Endo T., Nakazato M., Kogai T., Onaya T. Thyroid-stimulating hormone-induced down-regulation of thyroid transcription factor 1 in rat thyroid FRTL-5 cells. Endocrinology. 1997 Feb;138(2):602–606. doi: 10.1210/endo.138.2.4918. [DOI] [PubMed] [Google Scholar]
  19. Santisteban P., Acebrón A., Polycarpou-Schwarz M., Di Lauro R. Insulin and insulin-like growth factor I regulate a thyroid-specific nuclear protein that binds to the thyroglobulin promoter. Mol Endocrinol. 1992 Aug;6(8):1310–1317. doi: 10.1210/mend.6.8.1406708. [DOI] [PubMed] [Google Scholar]
  20. Shapiro D. J., Sharp P. A., Wahli W. W., Keller M. J. A high-efficiency HeLa cell nuclear transcription extract. DNA. 1988 Jan-Feb;7(1):47–55. doi: 10.1089/dna.1988.7.47. [DOI] [PubMed] [Google Scholar]
  21. Van Renterghem P., Vassart G., Christophe D. Pax 8 expression in primary cultured dog thyrocyte is increased by cyclic AMP. Biochim Biophys Acta. 1996 Jun 3;1307(1):97–103. doi: 10.1016/0167-4781(96)00018-8. [DOI] [PubMed] [Google Scholar]
  22. Zannini M., Francis-Lang H., Plachov D., Di Lauro R. Pax-8, a paired domain-containing protein, binds to a sequence overlapping the recognition site of a homeodomain and activates transcription from two thyroid-specific promoters. Mol Cell Biol. 1992 Sep;12(9):4230–4241. doi: 10.1128/mcb.12.9.4230. [DOI] [PMC free article] [PubMed] [Google Scholar]

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