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A c-erb-A binding site in rat growth hormone gene mediates trans-activation by thyroid hormone

Nature volume 329, pages 738–741 (1987)Cite this article

Abstract

The substance 3,5,3-triiodothyronine (T3) stimulates growth hormone gene transcription in rat pituitary tumour cells1–4. This stimulation is thought to be mediated by the binding of nuclear T3 receptors to regulatory elements 5' to the transcriptional start site5–8. Understanding of the mechanism by which thyroid hormone activates gene transcription has been limited by failure to purify nuclear T3 receptors because of their low abundance, and by the absence of defined T3 receptor-DNA binding sites affecting T3 regulation. Recently, human and avian c-erb-A gene products have been shown to bind thyroid hormone with high affinity9,10 and to have a molecular weight and nuclear association characteristic of the thyroid hormone receptor. In the present report, we describe the development of an avidin–biotin complex DNA-binding assay which can detect specific, high-affinity binding of rat pituitary cell T3 receptors to the sequence 5'CAGGGACGTGACCGCA3', located 164 base pairs 5' to the transcriptional start site of the rat growth hormone gene. An oligonucleotide containing this sequence transferred T3 regulation to the herpes simplex virus thymidine kinase promoter in transfected rat pituitary GC2 cells, and specifically bound an in vitro translation product of the human placental c-erb-A gene. The data provide supporting evidence that the human c-erb-A gene product mediates the transcriptional effects of T3 and also that GC2 cell nuclear extracts contain additional factors that modify the binding of pituitary T3 receptors to the rat growth hormone gene T3 response element.

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References

  1. Evans, R. M., Birnberg, N. C. & Rosenfeld, M. G. Proc. natn. Acad. Sci. U.S.A. 79, 7659–7663 (1982).

    Article  ADS  CAS  Google Scholar 

  2. Diamond, D. J. & Goodman, H. M. J. molec. Biol. 181, 41–62 (1985).

    Article  CAS  Google Scholar 

  3. Spindler, S. R., Mellon, S. H. & Baxter, J. D. J. biol. Chem. 257, 11627–11632 (1982).

    CAS  PubMed  Google Scholar 

  4. Yaffee, B. M. & Samuels, H. H. J. biol. Chem. 259, 6284–6291 (1984).

    Google Scholar 

  5. Larsen, P. R., Harney, J. W. & Moore, D. D. J. biol. Chem. 261, 14373–14376 (1986).

    CAS  PubMed  Google Scholar 

  6. Flug, F. et al. J. biol. Chem. 262, 6373–6382 (1987).

    CAS  PubMed  Google Scholar 

  7. Casanova, J., Copp, R. P., Janocko, L. & Samuels, H. H. J. biol. Chem. 260, 11744–11748 (1985).

    CAS  PubMed  Google Scholar 

  8. Crew, M. & Spindler, S. R. J. biol. Chem. 261, 5018–5022 (1986).

    CAS  PubMed  Google Scholar 

  9. Sap, J. et al. Nature 324, 635–640 (1986).

    Article  ADS  CAS  Google Scholar 

  10. Weinberger, C. et al. Nature 324, 641–646 (1986).

    Article  ADS  CAS  Google Scholar 

  11. Nelson, C. et al. Nature 322, 557–562 (1986).

    Article  ADS  CAS  Google Scholar 

  12. Elsholtz, H. P. et al. Science 234, 1552–1557 (1986).

    Article  ADS  CAS  Google Scholar 

  13. West, B. L. et al. Molec. cell. Biol. 7, 1193–1197 (1987).

    Article  CAS  Google Scholar 

  14. Catanzaro, D. F., West, B. L., Baxter, J. D. & Reudelhuber, T. L. Molec. Endocr. 1, 90–96 (1987).

    Article  CAS  Google Scholar 

  15. Nyborg, J. K. & Spindler, S. R. J. biol. Chem. 261, 5685–5688 (1986).

    CAS  PubMed  Google Scholar 

  16. Topol, J., Ruden, D. M. & Parker, C. S. Cell, 42, 527–537 (1985).

    Article  CAS  Google Scholar 

  17. Reinberg, D., Horikoshi, M. & Roeder, R. G. J. biol. Chem. 262, 3322–3330 (1987).

    CAS  PubMed  Google Scholar 

  18. McKnight, S. & Tjian, R. Cell 46, 795–805 (1986).

    Article  CAS  Google Scholar 

  19. Gorman, C. M., Moffat, L. F. & Howard, B. H. Molec. cell. Biol. 2, 1044–1051 (1982).

    Article  CAS  Google Scholar 

  20. Linney, E. & Donerly, S. Cell 35, 693–699 (1983).

    Article  CAS  Google Scholar 

  21. Kunkel, T. Proc. natn. Acad. Sci. U.S.A. 82, 488–492 (1985).

    Article  ADS  CAS  Google Scholar 

  22. Dingham, J. D., Lebovitz, R. M. & Roeder, R. G. Nucleic Acids Res. 11, 1475–1489 (1983).

    Article  Google Scholar 

  23. Samuels, H. H., Tsai, J. S., Casanova, J. & Stanley, F. J. clin. Invest. 54, 853–865 (1974).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Centre for Molecular Genetics, Eukaryotic Regulatory Biology Program, School of Medicine, University of California, San Diego, La Jolla, California, 92093, USA

    Christopher K. Glass, Rodrigo Franco, Vivian R. Albert & Michael G. Rosenfeld

  2. Department of Biology, Eukaryotic Regulatory Biology Program, School of Medicine, University of California, San Diego, La Jolla, California, 92093, USA

    Rodrigo Franco

  3. Salk Institute, La Jolla, California, 92037, USA

    Cary Weinberger & Ronald M. Evans

  4. Howard Hughes Medical Institute,

    Ronald M. Evans & Michael G. Rosenfeld

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  1. Christopher K. Glass
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  6. Michael G. Rosenfeld
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Glass, C., Franco, R., Weinberger, C. et al. A c-erb-A binding site in rat growth hormone gene mediates trans-activation by thyroid hormone. Nature 329, 738–741 (1987). https://doi.org/10.1038/329738a0

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