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. 1991 Oct;11(10):5005–5015. doi: 10.1128/mcb.11.10.5005

Differential DNA binding by monomeric, homodimeric, and potentially heteromeric forms of the thyroid hormone receptor.

M A Lazar 1, T J Berrodin 1, H P Harding 1
PMCID: PMC361489  PMID: 1922030

Abstract

Binding of the thyroid hormone receptor (TR) to thyroid hormone-responsive elements (TREs) is crucial for regulation of gene expression by thyroid hormone. The TR binds to each half-site of a palindromic TRE separately, as a monomer, or simultaneously, as a homodimer. In addition, the TR monomer interacts with a 42-kDa protein that may be responsible for an increase in the apparent size and stability of the TR-TRE complex after incubation with liver nuclear extract. The multiple DNA-binding forms of the TR contact the TRE differently but compete for binding in a dynamic equilibrium which is highly dependent on the relative concentrations of TR and nuclear protein. Thus, protein-protein interactions are likely to determine the context in which the TR binds to target genes and regulates the transcriptional response to thyroid hormone.

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Selected References

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

  1. Abate C., Patel L., Rauscher F. J., 3rd, Curran T. Redox regulation of fos and jun DNA-binding activity in vitro. Science. 1990 Sep 7;249(4973):1157–1161. doi: 10.1126/science.2118682. [DOI] [PubMed] [Google Scholar]
  2. Beebe J. S., Darling D. S., Chin W. W. 3,5,3'-triiodothyronine receptor auxiliary protein (TRAP) enhances receptor binding by interactions within the thyroid hormone response element. Mol Endocrinol. 1991 Jan;5(1):85–93. doi: 10.1210/mend-5-1-85. [DOI] [PubMed] [Google Scholar]
  3. Benezra R., Davis R. L., Lockshon D., Turner D. L., Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990 Apr 6;61(1):49–59. doi: 10.1016/0092-8674(90)90214-y. [DOI] [PubMed] [Google Scholar]
  4. Blackwell T. K., Weintraub H. Differences and similarities in DNA-binding preferences of MyoD and E2A protein complexes revealed by binding site selection. Science. 1990 Nov 23;250(4984):1104–1110. doi: 10.1126/science.2174572. [DOI] [PubMed] [Google Scholar]
  5. Brent G. A., Dunn M. K., Harney J. W., Gulick T., Larsen P. R., Moore D. D. Thyroid hormone aporeceptor represses T3-inducible promoters and blocks activity of the retinoic acid receptor. New Biol. 1989 Dec;1(3):329–336. [PubMed] [Google Scholar]
  6. Brent G. A., Harney J. W., Chen Y., Warne R. L., Moore D. D., Larsen P. R. Mutations of the rat growth hormone promoter which increase and decrease response to thyroid hormone define a consensus thyroid hormone response element. Mol Endocrinol. 1989 Dec;3(12):1996–2004. doi: 10.1210/mend-3-12-1996. [DOI] [PubMed] [Google Scholar]
  7. Burnside J., Darling D. S., Chin W. W. A nuclear factor that enhances binding of thyroid hormone receptors to thyroid hormone response elements. J Biol Chem. 1990 Feb 15;265(5):2500–2504. [PubMed] [Google Scholar]
  8. Chiu R., Boyle W. J., Meek J., Smeal T., Hunter T., Karin M. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell. 1988 Aug 12;54(4):541–552. doi: 10.1016/0092-8674(88)90076-1. [DOI] [PubMed] [Google Scholar]
  9. Cohen D. R., Ferreira P. C., Gentz R., Franza B. R., Jr, Curran T. The product of a fos-related gene, fra-1, binds cooperatively to the AP-1 site with Jun: transcription factor AP-1 is comprised of multiple protein complexes. Genes Dev. 1989 Feb;3(2):173–184. doi: 10.1101/gad.3.2.173. [DOI] [PubMed] [Google Scholar]
  10. Damm K., Thompson C. C., Evans R. M. Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist. Nature. 1989 Jun 22;339(6226):593–597. doi: 10.1038/339593a0. [DOI] [PubMed] [Google Scholar]
  11. Darling D. S., Beebe J. S., Burnside J., Winslow E. R., Chin W. W. 3,5,3'-triiodothyronine (T3) receptor-auxiliary protein (TRAP) binds DNA and forms heterodimers with the T3 receptor. Mol Endocrinol. 1991 Jan;5(1):73–84. doi: 10.1210/mend-5-1-73. [DOI] [PubMed] [Google Scholar]
  12. Diamond M. I., Miner J. N., Yoshinaga S. K., Yamamoto K. R. Transcription factor interactions: selectors of positive or negative regulation from a single DNA element. Science. 1990 Sep 14;249(4974):1266–1272. doi: 10.1126/science.2119054. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Fawell S. E., Lees J. A., White R., Parker M. G. Characterization and colocalization of steroid binding and dimerization activities in the mouse estrogen receptor. Cell. 1990 Mar 23;60(6):953–962. doi: 10.1016/0092-8674(90)90343-d. [DOI] [PubMed] [Google Scholar]
  16. Forman B. M., Samuels H. H. Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model. Mol Endocrinol. 1990 Sep;4(9):1293–1301. doi: 10.1210/mend-4-9-1293. [DOI] [PubMed] [Google Scholar]
  17. Forman B. M., Yang C. R., Au M., Casanova J., Ghysdael J., Samuels H. H. A domain containing leucine-zipper-like motifs mediate novel in vivo interactions between the thyroid hormone and retinoic acid receptors. Mol Endocrinol. 1989 Oct;3(10):1610–1626. doi: 10.1210/mend-3-10-1610. [DOI] [PubMed] [Google Scholar]
  18. Gaub M. P., Bellard M., Scheuer I., Chambon P., Sassone-Corsi P. Activation of the ovalbumin gene by the estrogen receptor involves the fos-jun complex. Cell. 1990 Dec 21;63(6):1267–1276. doi: 10.1016/0092-8674(90)90422-b. [DOI] [PubMed] [Google Scholar]
  19. Glass C. K., Devary O. V., Rosenfeld M. G. Multiple cell type-specific proteins differentially regulate target sequence recognition by the alpha retinoic acid receptor. Cell. 1990 Nov 16;63(4):729–738. doi: 10.1016/0092-8674(90)90139-6. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Glass C. K., Lipkin S. M., Devary O. V., Rosenfeld M. G. Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer. Cell. 1989 Nov 17;59(4):697–708. doi: 10.1016/0092-8674(89)90016-0. [DOI] [PubMed] [Google Scholar]
  22. Graupner G., Wills K. N., Tzukerman M., Zhang X. K., Pfahl M. Dual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity. Nature. 1989 Aug 24;340(6235):653–656. doi: 10.1038/340653a0. [DOI] [PubMed] [Google Scholar]
  23. Green S., Chambon P. Nuclear receptors enhance our understanding of transcription regulation. Trends Genet. 1988 Nov;4(11):309–314. doi: 10.1016/0168-9525(88)90108-4. [DOI] [PubMed] [Google Scholar]
  24. Halazonetis T. D., Georgopoulos K., Greenberg M. E., Leder P. c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. Cell. 1988 Dec 2;55(5):917–924. doi: 10.1016/0092-8674(88)90147-x. [DOI] [PubMed] [Google Scholar]
  25. Hodin R. A., Lazar M. A., Wintman B. I., Darling D. S., Koenig R. J., Larsen P. R., Moore D. D., Chin W. W. Identification of a thyroid hormone receptor that is pituitary-specific. Science. 1989 Apr 7;244(4900):76–79. doi: 10.1126/science.2539642. [DOI] [PubMed] [Google Scholar]
  26. Holloway J. M., Glass C. K., Adler S., Nelson C. A., Rosenfeld M. G. The C'-terminal interaction domain of the thyroid hormone receptor confers the ability of the DNA site to dictate positive or negative transcriptional activity. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8160–8164. doi: 10.1073/pnas.87.20.8160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hudson L. G., Santon J. B., Glass C. K., Gill G. N. Ligand-activated thyroid hormone and retinoic acid receptors inhibit growth factor receptor promoter expression. Cell. 1990 Sep 21;62(6):1165–1175. doi: 10.1016/0092-8674(90)90393-s. [DOI] [PubMed] [Google Scholar]
  28. Jonat C., Rahmsdorf H. J., Park K. K., Cato A. C., Gebel S., Ponta H., Herrlich P. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell. 1990 Sep 21;62(6):1189–1204. doi: 10.1016/0092-8674(90)90395-u. [DOI] [PubMed] [Google Scholar]
  29. Koenig R. J., Warne R. L., Brent G. A., Harney J. W., Larsen P. R., Moore D. D. Isolation of a cDNA clone encoding a biologically active thyroid hormone receptor. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5031–5035. doi: 10.1073/pnas.85.14.5031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Ladias J. A., Karathanasis S. K. Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily. Science. 1991 Feb 1;251(4993):561–565. doi: 10.1126/science.1899293. [DOI] [PubMed] [Google Scholar]
  32. Lazar M. A., Berrodin T. J. Thyroid hormone receptors form distinct nuclear protein-dependent and independent complexes with a thyroid hormone response element. Mol Endocrinol. 1990 Nov;4(11):1627–1635. doi: 10.1210/mend-4-11-1627. [DOI] [PubMed] [Google Scholar]
  33. Lazar M. A., Chin W. W. Nuclear thyroid hormone receptors. J Clin Invest. 1990 Dec;86(6):1777–1782. doi: 10.1172/JCI114906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lazar M. A., Hodin R. A., Darling D. S., Chin W. W. Identification of a rat c-erbA alpha-related protein which binds deoxyribonucleic acid but does not bind thyroid hormone. Mol Endocrinol. 1988 Oct;2(10):893–901. doi: 10.1210/mend-2-10-893. [DOI] [PubMed] [Google Scholar]
  35. Lees J. A., Fawell S. E., White R., Parker M. G. A 22-amino-acid peptide restores DNA-binding activity to dimerization-defective mutants of the estrogen receptor. Mol Cell Biol. 1990 Oct;10(10):5529–5531. doi: 10.1128/mcb.10.10.5529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Lewin B. Commitment and activation at pol II promoters: a tail of protein-protein interactions. Cell. 1990 Jun 29;61(7):1161–1164. doi: 10.1016/0092-8674(90)90675-5. [DOI] [PubMed] [Google Scholar]
  37. Liao J., Ozono K., Sone T., McDonnell D. P., Pike J. W. Vitamin D receptor interaction with specific DNA requires a nuclear protein and 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9751–9755. doi: 10.1073/pnas.87.24.9751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mukherjee R., Chambon P. A single-stranded DNA-binding protein promotes the binding of the purified oestrogen receptor to its responsive element. Nucleic Acids Res. 1990 Oct 11;18(19):5713–5716. doi: 10.1093/nar/18.19.5713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Murray M. B., Towle H. C. Identification of nuclear factors that enhance binding of the thyroid hormone receptor to a thyroid hormone response element. Mol Endocrinol. 1989 Sep;3(9):1434–1442. doi: 10.1210/mend-3-9-1434. [DOI] [PubMed] [Google Scholar]
  40. Nakabeppu Y., Ryder K., Nathans D. DNA binding activities of three murine Jun proteins: stimulation by Fos. Cell. 1988 Dec 2;55(5):907–915. doi: 10.1016/0092-8674(88)90146-8. [DOI] [PubMed] [Google Scholar]
  41. O'Donnell A. L., Rosen E. D., Darling D. S., Koenig R. J. Thyroid hormone receptor mutations that interfere with transcriptional activation also interfere with receptor interaction with a nuclear protein. Mol Endocrinol. 1991 Jan;5(1):94–99. doi: 10.1210/mend-5-1-94. [DOI] [PubMed] [Google Scholar]
  42. Ptashne M. How eukaryotic transcriptional activators work. Nature. 1988 Oct 20;335(6192):683–689. doi: 10.1038/335683a0. [DOI] [PubMed] [Google Scholar]
  43. Rauscher F. J., 3rd, Voulalas P. J., Franza B. R., Jr, Curran T. Fos and Jun bind cooperatively to the AP-1 site: reconstitution in vitro. Genes Dev. 1988 Dec;2(12B):1687–1699. doi: 10.1101/gad.2.12b.1687. [DOI] [PubMed] [Google Scholar]
  44. 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]
  45. 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]
  46. Sassone-Corsi P., Lamph W. W., Kamps M., Verma I. M. fos-associated cellular p39 is related to nuclear transcription factor AP-1. Cell. 1988 Aug 12;54(4):553–560. doi: 10.1016/0092-8674(88)90077-3. [DOI] [PubMed] [Google Scholar]
  47. Schüle R., Rangarajan P., Kliewer S., Ransone L. J., Bolado J., Yang N., Verma I. M., Evans R. M. Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell. 1990 Sep 21;62(6):1217–1226. doi: 10.1016/0092-8674(90)90397-w. [DOI] [PubMed] [Google Scholar]
  48. Studier F. W., Rosenberg A. H., Dunn J. J., Dubendorff J. W. Use of T7 RNA polymerase to direct expression of cloned genes. Methods Enzymol. 1990;185:60–89. doi: 10.1016/0076-6879(90)85008-c. [DOI] [PubMed] [Google Scholar]
  49. Surks M. I., Koerner D., Dillman W., Oppenheimer J. H. Limited capacity binding sites for L-triiodothyronine in rat liver nuclei. Localization to the chromatin and partial characterization of the L-triiodothyronine-chromatin complex. J Biol Chem. 1973 Oct 25;248(20):7066–7072. [PubMed] [Google Scholar]
  50. Wang L. H., Tsai S. Y., Cook R. G., Beattie W. G., Tsai M. J., O'Malley B. W. COUP transcription factor is a member of the steroid receptor superfamily. Nature. 1989 Jul 13;340(6229):163–166. doi: 10.1038/340163a0. [DOI] [PubMed] [Google Scholar]
  51. 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]
  52. Yang-Yen H. F., Chambard J. C., Sun Y. L., Smeal T., Schmidt T. J., Drouin J., Karin M. Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell. 1990 Sep 21;62(6):1205–1215. doi: 10.1016/0092-8674(90)90396-v. [DOI] [PubMed] [Google Scholar]
  53. Zerial M., Toschi L., Ryseck R. P., Schuermann M., Müller R., Bravo R. The product of a novel growth factor activated gene, fos B, interacts with JUN proteins enhancing their DNA binding activity. EMBO J. 1989 Mar;8(3):805–813. doi: 10.1002/j.1460-2075.1989.tb03441.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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