Summary
The molecular biology of thyroid hormone action has been studied by examining the binding of purified (ca 300-fold) rat liver thyroid hormone receptors to various DNAs, and the responsiveness to triiodothyronine (T3) of native and mutated rat growth hormone (rGH), and human GH (hGH) and placental lactogen (hCS) DNA fragments linked to chloramphenicol acetyltransferase (CAT) or other reporter gene sequences transfected into cultured rat pituitary tumor (GC) cells. The receptors bind specifically to four different sequences within the rGH 5’-flanking DNA from −237/+1 centered at ca. −180, −160, −60 and −20 with respect to the transcriptional start site. Each of these sites appears to contribute to positive T3 responsiveness of the rGH promoter and the various sites can interact synergistically to generate the response. Although the hCS 5’-flanking DNA is positively T3 responsive, the highly homologous (>90%) hGH gene is regulated negatively by T3; this negative responsiveness involves hGH DNA elements located downstream from the transcriptional start site as well as 5’-flanking DNA elements that interact in an as yet undefined manner. Specific receptor binding to a number of other T3 responsive genes was also found. Alignment of the receptor binding sequences suggests an overall structure spanning ca. 20 bp that includes a conserved region on the 3’-end that is comprised of GGGT AC and a less conserved region on the 5’-end that contains AAGA as the more frequently occurring nucleotides. T3 was not found to affect receptor binding to specific sequences. However, evidence for receptor-induced bending of DNA was obtained which also correlated with T3 responsiveness. These results suggest an emerging pattern for DNA recognition by thyroid hormone receptors and emphasize the role of multiple DNA sequences in generating T3 responsiveness.
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References
Apriletti, J., Baxter J., and Lavin T.N. (1988) J. Biol. Chem. 263, 9409–9417.
Apriletti, J.W., Eberhardt, N.L., and’Baxter, J.D. (1983) In: Molecular Basis of Thyroid Hormone Action, (J.H. Oppenheimer and H.H. Samuels, Eds), Academic Press, New York, pp. 67–97.
Beato, M., Arnemann, J., Chalepakis, G., Slater, E., and Willmann, T. (1987) J. Steroid Biochem. 27, 9–14.
Casanova, J., Copp, R.P., Janocko, L., and Samuels, H.H. (1985) J. Biol. Chem. 260, 11744–11748.
Cattini, P.A., Anderson, T.R., Baxter, J.D., Mellon, P., and Eberhardt, N.L. (1986) J. Biol. Chem. 261, 13367–13372.
Chalepakis, G., Postma, J.P.M., and Beato, M. (1988) Nucl. Acids Res. 16, 10237–10247.
Glass, C.K., Holloway, J.M., Devary, O.V., and Rosenfeld, M.G. (1988) Cell 54, 313–323.
Groyer, A., Schweizer-Groyer, G., Cadepond, F., Marller, M., and Baulieu, E-E. (1987) Nature 328, 624–626.
Ham, J., Thomson, A., Needham, M., Webb, P., and Parker, M. (1988) Nucleic Acids Res. 12, 5263–5276.
Kumar, V., and Chambon, P. (1988) Cell 55, 145–156.
Larsen, P.R., Harney, J.W., and Moore, D.D. (1986) J. Biol. Chem. 261, 14373–14376.
Lavin, T.N. (1988) In: Endocrinology, 2nd Edition, ( L. DeGroot, Ed. ), Grune and Stratteon, pp 562–573.
Lavin, T.N., and Horito S. (1988) J. Biol. Chem. 263, 9418–9425.
Martial, J.A., Seeburg, P.H., Guenzi, D., Goodman, H.M., and Baxter, J.D. (1977) Proc. Natl. Acad. Sci., USA 90, 4293–2495.
Melmed, S., and Salmima, S. (1985) Endocrinology 117, 532–537.
Norman, M.F., Lavin, T.N., Baxter, J.D., and West, B.L., submitted for publication.
Ptashne, M. (1986) Nature 322, 697–701.
Sakai, D.D., Helms, S., Carlstedt-Duke, J., Gustafsson, J-A., Rottman, F.M., and Yamamoto, K.R. (1988) Genes and Development 2, 1144–1154.
Samuels, H.H., Forman, B.M., Horowitz, Z.D., and Ye, Z-S. (1988) J. Clin. Invest. 81, 957–967.
Scheidereit, C., and Beato, M. (1984) Proc. Natl. Acad. Sci. USA 81, 3029–3033.
Silva, J.E., and Oppenheimer, J.A. (1977) J. Biol. Chem. 252, 6799–6805.
Spindler, B.J., MacLeod, K.M., Ring, J., and Baxter, J.D. (1975) J. Biol. Chem. 250, 4113–4119.
Tsai, S.Y., Carlstedt-Duke, J., Weigel, N.L., Dahlman, K., Gustafsson, J-A., Tsai, M-J, and O’Malley, B.W. (1988) Cell 55, 361–369.
Umesono, K., Giguere, V., Glass, C.K., Rosenfeld, M.G., and Evans, R.G. (1988) Nature 336, 262–264.
West, B.L., Catanzaro, D.F., Mellon, S.H., Cattini, P., Baxter, J.D., and Reudelhuber, T.L. (1987) Mol. Cell. Biol. 1, 1193–1197.
Wight, P.A., Crew, M.D., and Spindler, S.R. (1987) J. Biol. Chem. 262, 5659–5663.
Ye, Z-S., Forman, B.M., Aranda, A., Pascual, A., Park, H-Y., Casanova, J., and Samuels, H.H. (1988) J. Biol. Chem. 263, 7821–7829.
Ye, Z-S., and Samuels, H.H. (1987) J. Biol. Chem. 262, 6313–6317.
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Lavin, T.N., Norman, M.F., Eberhardt, N., Baxter, J.D. (1989). Thyroid Hormone Receptor Interactions with DNA. In: Carlstedt-Duke, J., Eriksson, H., Gustafsson, JÅ. (eds) The Steroid/Thyroid Hormone Receptor Family and Gene Regulation. Birkhäuser Congress Reports Life Sciences. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-5466-5_5
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DOI: https://doi.org/10.1007/978-3-0348-5466-5_5
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