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. 1990 Mar;9(3):887–896. doi: 10.1002/j.1460-2075.1990.tb08186.x

A major thyroid hormone response element in the third intron of the rat growth hormone gene.

J Sap 1, L de Magistris 1, H Stunnenberg 1, B Vennström 1
PMCID: PMC551749  PMID: 2155782

Abstract

The rat growth hormone (RGH) gene constitutes a well-documented model system for the direct regulation of transcription by thyroid hormones. In order to analyse its interaction with sequences in the RGH gene, we have overproduced the thyroid hormone receptor-alpha (c-erbA) protein using a vaccinia virus expression system. The expressed protein bound T3 and DNA-cellulose with expected affinities, and the major binding site for the receptor protein was found to be located in the third intron of the RGH gene. This site displayed significantly higher affinity for the receptor protein than a previously described thyroid hormone response element (TRE) in the promoter of this gene, and also conferred stronger hormone responsiveness in vivo to a heterologous promoter. The data suggest that this novel TRE plays a major role in the regulation of rat growth hormone gene expression by thyroid hormones.

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Selected References

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  1. Barta A., Richards R. I., Baxter J. D., Shine J. Primary structure and evolution of rat growth hormone gene. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4867–4871. doi: 10.1073/pnas.78.8.4867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. doi: 10.1016/0092-8674(89)90237-7. [DOI] [PubMed] [Google Scholar]
  3. Benbrook D., Pfahl M. A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library. Science. 1987 Nov 6;238(4828):788–791. doi: 10.1126/science.3672126. [DOI] [PubMed] [Google Scholar]
  4. Berg J. M. Potential metal-binding domains in nucleic acid binding proteins. Science. 1986 Apr 25;232(4749):485–487. doi: 10.1126/science.2421409. [DOI] [PubMed] [Google Scholar]
  5. Birnbaum M. J., Baxter J. D. Glucocorticoids regulate the expression of a rat growth hormone gene lacking 5' flanking sequences. J Biol Chem. 1986 Jan 5;261(1):291–297. [PubMed] [Google Scholar]
  6. Breathnach R., Harris B. A. Plasmids for the cloning and expression of full-length double-stranded cDNAs under control of the SV40 early or late gene promoter. Nucleic Acids Res. 1983 Oct 25;11(20):7119–7136. doi: 10.1093/nar/11.20.7119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brinster R. L., Allen J. M., Behringer R. R., Gelinas R. E., Palmiter R. D. Introns increase transcriptional efficiency in transgenic mice. Proc Natl Acad Sci U S A. 1988 Feb;85(3):836–840. doi: 10.1073/pnas.85.3.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Denis M., Poellinger L., Wikstöm A. C., Gustafsson J. A. Requirement of hormone for thermal conversion of the glucocorticoid receptor to a DNA-binding state. Nature. 1988 Jun 16;333(6174):686–688. doi: 10.1038/333686a0. [DOI] [PubMed] [Google Scholar]
  9. Evans R. M., Hollenberg S. M. Zinc fingers: gilt by association. Cell. 1988 Jan 15;52(1):1–3. doi: 10.1016/0092-8674(88)90522-3. [DOI] [PubMed] [Google Scholar]
  10. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Flug F., Copp R. P., Casanova J., Horowitz Z. D., Janocko L., Plotnick M., Samuels H. H. cis-acting elements of the rat growth hormone gene which mediate basal and regulated expression by thyroid hormone. J Biol Chem. 1987 May 5;262(13):6373–6382. [PubMed] [Google Scholar]
  12. Freedman L. P., Luisi B. F., Korszun Z. R., Basavappa R., Sigler P. B., Yamamoto K. R. The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain. Nature. 1988 Aug 11;334(6182):543–546. doi: 10.1038/334543a0. [DOI] [PubMed] [Google Scholar]
  13. Glass C. K., Franco R., Weinberger C., Albert V. R., Evans R. M., Rosenfeld M. G. A c-erb-A binding site in rat growth hormone gene mediates trans-activation by thyroid hormone. Nature. 1987 Oct 22;329(6141):738–741. doi: 10.1038/329738a0. [DOI] [PubMed] [Google Scholar]
  14. Glass C. K., Holloway J. M., Devary O. V., Rosenfeld M. G. The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements. Cell. 1988 Jul 29;54(3):313–323. doi: 10.1016/0092-8674(88)90194-8. [DOI] [PubMed] [Google Scholar]
  15. Goldberg Y., Glineur C., Gesquière J. C., Ricouart A., Sap J., Vennström B., Ghysdael J. Activation of protein kinase C or cAMP-dependent protein kinase increases phosphorylation of the c-erbA-encoded thyroid hormone receptor and of the v-erbA-encoded protein. EMBO J. 1988 Aug;7(8):2425–2433. doi: 10.1002/j.1460-2075.1988.tb03088.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Green S., Chambon P. Oestradiol induction of a glucocorticoid-responsive gene by a chimaeric receptor. Nature. 1987 Jan 1;325(6099):75–78. doi: 10.1038/325075a0. [DOI] [PubMed] [Google Scholar]
  17. Groyer A., Schweizer-Groyer G., Cadepond F., Mariller M., Baulieu E. E. Antiglucocorticosteroid effects suggest why steroid hormone is required for receptors to bind DNA in vivo but not in vitro. Nature. 1987 Aug 13;328(6131):624–626. doi: 10.1038/328624a0. [DOI] [PubMed] [Google Scholar]
  18. Grundström T., Zenke W. M., Wintzerith M., Matthes H. W., Staub A., Chambon P. Oligonucleotide-directed mutagenesis by microscale 'shot-gun' gene synthesis. Nucleic Acids Res. 1985 May 10;13(9):3305–3316. doi: 10.1093/nar/13.9.3305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Izumo S., Mahdavi V. Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription. Nature. 1988 Aug 11;334(6182):539–542. doi: 10.1038/334539a0. [DOI] [PubMed] [Google Scholar]
  20. Jantzen H. M., Strähle U., Gloss B., Stewart F., Schmid W., Boshart M., Miksicek R., Schütz G. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell. 1987 Apr 10;49(1):29–38. doi: 10.1016/0092-8674(87)90752-5. [DOI] [PubMed] [Google Scholar]
  21. Koenig R. J., Brent G. A., Warne R. L., Larsen P. R., Moore D. D. Thyroid hormone receptor binds to a site in the rat growth hormone promoter required for induction by thyroid hormone. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5670–5674. doi: 10.1073/pnas.84.16.5670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  23. Kumar V., Chambon P. The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer. Cell. 1988 Oct 7;55(1):145–156. doi: 10.1016/0092-8674(88)90017-7. [DOI] [PubMed] [Google Scholar]
  24. Larsen P. R., Harney J. W., Moore D. D. Sequences required for cell-type specific thyroid hormone regulation of rat growth hormone promoter activity. J Biol Chem. 1986 Nov 5;261(31):14373–14376. [PubMed] [Google Scholar]
  25. Lavin T. N., Baxter J. D., Horita S. The thyroid hormone receptor binds to multiple domains of the rat growth hormone 5'-flanking sequence. J Biol Chem. 1988 Jul 5;263(19):9418–9426. [PubMed] [Google Scholar]
  26. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Martial J. A., Seeburg P. H., Guenzi D., Goodman H. M., Baxter J. D. Regulation of growth hormone gene expression: synergistic effects of thyroid and glucocorticoid hormones. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4293–4295. doi: 10.1073/pnas.74.10.4293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Murray M. B., Zilz N. D., McCreary N. L., MacDonald M. J., Towle H. C. Isolation and characterization of rat cDNA clones for two distinct thyroid hormone receptors. J Biol Chem. 1988 Sep 5;263(25):12770–12777. [PubMed] [Google Scholar]
  29. Picard D., Yamamoto K. R. Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor. EMBO J. 1987 Nov;6(11):3333–3340. doi: 10.1002/j.1460-2075.1987.tb02654.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Samuels H. H., Forman B. M., Horowitz Z. D., Ye Z. S. Regulation of gene expression by thyroid hormone. J Clin Invest. 1988 Apr;81(4):957–967. doi: 10.1172/JCI113449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sap J., Muñoz A., Damm K., Goldberg Y., Ghysdael J., Leutz A., Beug H., Vennström B. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986 Dec 18;324(6098):635–640. doi: 10.1038/324635a0. [DOI] [PubMed] [Google Scholar]
  32. Slater E. P., Rabenau O., Karin M., Baxter J. D., Beato M. Glucocorticoid receptor binding and activation of a heterologous promoter by dexamethasone by the first intron of the human growth hormone gene. Mol Cell Biol. 1985 Nov;5(11):2984–2992. doi: 10.1128/mcb.5.11.2984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Stunnenberg H. G., Lange H., Philipson L., van Miltenburg R. T., van der Vliet P. C. High expression of functional adenovirus DNA polymerase and precursor terminal protein using recombinant vaccinia virus. Nucleic Acids Res. 1988 Mar 25;16(6):2431–2444. doi: 10.1093/nar/16.6.2431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Thompson C. C., Weinberger C., Lebo R., Evans R. M. Identification of a novel thyroid hormone receptor expressed in the mammalian central nervous system. Science. 1987 Sep 25;237(4822):1610–1614. doi: 10.1126/science.3629259. [DOI] [PubMed] [Google Scholar]
  35. Umesono K., Giguere V., Glass C. K., Rosenfeld M. G., Evans R. M. Retinoic acid and thyroid hormone induce gene expression through a common responsive element. Nature. 1988 Nov 17;336(6196):262–265. doi: 10.1038/336262a0. [DOI] [PubMed] [Google Scholar]
  36. Webster N. J., Green S., Jin J. R., Chambon P. The hormone-binding domains of the estrogen and glucocorticoid receptors contain an inducible transcription activation function. Cell. 1988 Jul 15;54(2):199–207. doi: 10.1016/0092-8674(88)90552-1. [DOI] [PubMed] [Google Scholar]
  37. Weinberger C., Thompson C. C., Ong E. S., Lebo R., Gruol D. J., Evans R. M. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986 Dec 18;324(6098):641–646. doi: 10.1038/324641a0. [DOI] [PubMed] [Google Scholar]
  38. de Magistris L., Stunnenberg H. G. Cis-acting sequences affecting the length of the poly(A) head of vaccinia virus late transcripts. Nucleic Acids Res. 1988 Apr 25;16(8):3141–3156. doi: 10.1093/nar/16.8.3141. [DOI] [PMC free article] [PubMed] [Google Scholar]

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