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. 1989 Sep;8(9):2537–2542. doi: 10.1002/j.1460-2075.1989.tb08391.x

A thyroid-specific nuclear protein essential for tissue-specific expression of the thyroglobulin promoter.

D Civitareale 1, R Lonigro 1, A J Sinclair 1, R Di Lauro 1
PMCID: PMC401250  PMID: 2583123

Abstract

A rat thyroglobulin promoter fragment, capable of directing thyroid-specific transcription, binds at least three different factors, TTF-1, TTF-2 and UFA, which are all present in nuclear extracts of the differentiated rat thyroid cell line FRTL-5. TTF-1 and TTF-2 are FRTL-5 specific, as demonstrated by their absence in nuclear extracts prepared from cell lines that do not express any thyroid-differentiated function, while UFA is present in all cell lines tested. TTF-1 has been extensively purified. It binds to the rat thyroglobulin promoter at three different sites which share sequence homology. Mutations in two of the three sites decrease both binding of TTF-1 in vitro and promoter function in vivo. This suggests that the tissue-specific expression of the thyroglobulin genes is mediated, at least in part, by the presence of a transcription factor exclusively in thyroid cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ambesi-Impiombato F. S., Parks L. A., Coon H. G. Culture of hormone-dependent functional epithelial cells from rat thyroids. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3455–3459. doi: 10.1073/pnas.77.6.3455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Atchison M. L., Perry R. P. The role of the kappa enhancer and its binding factor NF-kappa B in the developmental regulation of kappa gene transcription. Cell. 1987 Jan 16;48(1):121–128. doi: 10.1016/0092-8674(87)90362-x. [DOI] [PubMed] [Google Scholar]
  3. Avvedimento V. E., Monticelli A., Tramontano D., Polistina C., Nitsch L., Di Lauro R. Differential expression of thyroglobulin gene in normal and transformed thyroid cells. Eur J Biochem. 1985 Jun 18;149(3):467–472. doi: 10.1111/j.1432-1033.1985.tb08948.x. [DOI] [PubMed] [Google Scholar]
  4. Avvedimento V. E., Musti A., Fusco A., Bonapace M. J., Di Lauro R. Neoplastic transformation inactivates specific trans-acting factor(s) required for the expression of the thyroglobulin gene. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1744–1748. doi: 10.1073/pnas.85.6.1744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Avvedimento V. E., Tramontano D., Ursini M. V., Monticelli A., Di Lauro R. The level of thyroglobulin mRNA is regulated by TSH both in vitro and in vivo. Biochem Biophys Res Commun. 1984 Jul 18;122(1):472–477. doi: 10.1016/0006-291x(84)90500-x. [DOI] [PubMed] [Google Scholar]
  6. Banerji J., Olson L., Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. doi: 10.1016/0092-8674(83)90015-6. [DOI] [PubMed] [Google Scholar]
  7. Botchan M., Topp W., Sambrook J. The arrangement of simian virus 40 sequences in the DNA of transformed cells. Cell. 1976 Oct;9(2):269–287. doi: 10.1016/0092-8674(76)90118-5. [DOI] [PubMed] [Google Scholar]
  8. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Galas D. J., Schmitz A. DNAse footprinting: a simple method for the detection of protein-DNA binding specificity. Nucleic Acids Res. 1978 Sep;5(9):3157–3170. doi: 10.1093/nar/5.9.3157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gillies S. D., Morrison S. L., Oi V. T., Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983 Jul;33(3):717–728. doi: 10.1016/0092-8674(83)90014-4. [DOI] [PubMed] [Google Scholar]
  11. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  13. Ingraham H. A., Chen R. P., Mangalam H. J., Elsholtz H. P., Flynn S. E., Lin C. R., Simmons D. M., Swanson L., Rosenfeld M. G. A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell. 1988 Nov 4;55(3):519–529. doi: 10.1016/0092-8674(88)90038-4. [DOI] [PubMed] [Google Scholar]
  14. Kawaoi A., Tsuneda M. Functional development and maturation of the rat thyroid gland in the foetal and newborn periods: an immunohistochemical study. Acta Endocrinol (Copenh) 1985 Apr;108(4):518–524. doi: 10.1530/acta.0.1080518. [DOI] [PubMed] [Google Scholar]
  15. Kramer W., Drutsa V., Jansen H. W., Kramer B., Pflugfelder M., Fritz H. J. The gapped duplex DNA approach to oligonucleotide-directed mutation construction. Nucleic Acids Res. 1984 Dec 21;12(24):9441–9456. doi: 10.1093/nar/12.24.9441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lefevre C., Imagawa M., Dana S., Grindlay J., Bodner M., Karin M. Tissue-specific expression of the human growth hormone gene is conferred in part by the binding of a specific trans-acting factor. EMBO J. 1987 Apr;6(4):971–981. doi: 10.1002/j.1460-2075.1987.tb04847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lenardo M., Pierce J. W., Baltimore D. Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. Science. 1987 Jun 19;236(4808):1573–1577. doi: 10.1126/science.3109035. [DOI] [PubMed] [Google Scholar]
  18. Lichtsteiner S., Wuarin J., Schibler U. The interplay of DNA-binding proteins on the promoter of the mouse albumin gene. Cell. 1987 Dec 24;51(6):963–973. doi: 10.1016/0092-8674(87)90583-6. [DOI] [PubMed] [Google Scholar]
  19. Monaci P., Nicosia A., Cortese R. Two different liver-specific factors stimulate in vitro transcription from the human alpha 1-antitrypsin promoter. EMBO J. 1988 Jul;7(7):2075–2087. doi: 10.1002/j.1460-2075.1988.tb03047.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Musti A. M., Avvedimento E. V., Polistina C., Ursini V. M., Obici S., Nitsch L., Cocozza S., Di Lauro R. The complete structure of the rat thyroglobulin gene. Proc Natl Acad Sci U S A. 1986 Jan;83(2):323–327. doi: 10.1073/pnas.83.2.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Musti A. M., Ursini V. M., Avvedimento E. V., Zimarino V., Di Lauro R. A cell type specific factor recognizes the rat thyroglobulin promoter. Nucleic Acids Res. 1987 Oct 26;15(20):8149–8166. doi: 10.1093/nar/15.20.8149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Müller M. M., Ruppert S., Schaffner W., Matthias P. A cloned octamer transcription factor stimulates transcription from lymphoid-specific promoters in non-B cells. Nature. 1988 Dec 8;336(6199):544–551. doi: 10.1038/336544a0. [DOI] [PubMed] [Google Scholar]
  23. Nelson C., Albert V. R., Elsholtz H. P., Lu L. I., Rosenfeld M. G. Activation of cell-specific expression of rat growth hormone and prolactin genes by a common transcription factor. Science. 1988 Mar 18;239(4846):1400–1405. doi: 10.1126/science.2831625. [DOI] [PubMed] [Google Scholar]
  24. Queen C., Baltimore D. Immunoglobulin gene transcription is activated by downstream sequence elements. Cell. 1983 Jul;33(3):741–748. doi: 10.1016/0092-8674(83)90016-8. [DOI] [PubMed] [Google Scholar]
  25. Riccio A., Grimaldi G., Verde P., Sebastio G., Boast S., Blasi F. The human urokinase-plasminogen activator gene and its promoter. Nucleic Acids Res. 1985 Apr 25;13(8):2759–2771. doi: 10.1093/nar/13.8.2759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Santisteban P., Kohn L. D., Di Lauro R. Thyroglobulin gene expression is regulated by insulin and insulin-like growth factor I, as well as thyrotropin, in FRTL-5 thyroid cells. J Biol Chem. 1987 Mar 25;262(9):4048–4052. [PubMed] [Google Scholar]
  27. Schneider R., Gander I., Müller U., Mertz R., Winnacker E. L. A sensitive and rapid gel retention assay for nuclear factor I and other DNA-binding proteins in crude nuclear extracts. Nucleic Acids Res. 1986 Feb 11;14(3):1303–1317. doi: 10.1093/nar/14.3.1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Severne Y., Wieland S., Schaffner W., Rusconi S. Metal binding 'finger' structures in the glucocorticoid receptor defined by site-directed mutagenesis. EMBO J. 1988 Aug;7(8):2503–2508. doi: 10.1002/j.1460-2075.1988.tb03097.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Van Heuverswyn B., Streydio C., Brocas H., Refetoff S., Dumont J., Vassart G. Thyrotropin controls transcription of the thyroglobulin gene. Proc Natl Acad Sci U S A. 1984 Oct;81(19):5941–5945. doi: 10.1073/pnas.81.19.5941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Walker M. D., Edlund T., Boulet A. M., Rutter W. J. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. doi: 10.1038/306557a0. [DOI] [PubMed] [Google Scholar]
  32. de Wet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. doi: 10.1128/mcb.7.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]

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