Molecular Mechanisms of Nuclear Thyroid Hormone Action

  • William W. Chin
  • Paul M. Yen
Part of the Contemporary Endocrinology book series (COE, volume 2)


The role of thyroid hormone (l-triiodothyronine, T3; L-tetraiodothyronine, T4; TH) in the regulation of diverse cellular activities, including normal growth and development, and general metabolism, is well established (1–4). TH exerts its major effects at the genomic level, although action at nongenomic sites such as the plasma membrane, cytoplasm, mitochondrion, and so on, is also evident (see Chapter 2). Much work in the field, especially over the past decade, has developed a better understanding of the molecular mechanisms involved in TH action and gene transcription (5,6). As illustrated in Fig. 1, circulating free TH enters the cell by either passive diffusion or other yet poorly described mechanisms. In addition, the more biologically active T3 may be generated from T4 in some tissues by iodothyronine 5 ′-deiodinases, and both T3 and T4 may be subject to further intracellular inactivation. TH then enters the nucleus where it binds to the nuclear thyroid hormone receptor (TR) with high affinity and specificity (Kds in the nanomolar range). TR is a ligand-regulated transcription factor that is intimately associated with chromatin, and also associates with additional nuclear proteins to form heterodimers. These, in turn, are bound to target DNAs known as TH-response elements (TREs). The formation of a liganded TR/DNA complex leads to activation of its associated gene, and consequent changes in mRNA and protein. Thus, the central role of TR in nuclear TH action is evident.


Thyroid Hormone Retinoic Acid Retinoic Acid Receptor Thyroid Hormone Receptor Thyroid Hormone Action 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Oppenheimer J, Schwartz H, Mariash C, Kinlaw W, Wong N, Freake H. Advances in our understanding of thyroid hormone action at the cellular level. Endocr Rev 1987; 8: 288–308.PubMedCrossRefGoogle Scholar
  2. 2.
    Yen P, Chin W. New advances in understanding the molecular mechanisms of thyroid hormone action. Trends Endo Metab 1994; 5: 65–72.CrossRefGoogle Scholar
  3. 3.
    Glass C, Holloway J. Regulation of gene expression by the thyroid hormone receptor. Biochim Biophys Acta 1990; 1032: 157–176.PubMedGoogle Scholar
  4. 4.
    Brent G. The molecular basis of thyroid hormone action. N Engl J Med 1994; 331: 847–853.PubMedCrossRefGoogle Scholar
  5. 5.
    Lazar M, Chin W. Nuclear thyroid hormone receptors. J Clin Invest 1990; 86: 1777–1782.PubMedCrossRefGoogle Scholar
  6. 6.
    Lazar M. Thyroid hormone receptors: Multiple forms, multiple possibilities. Endocr Rev 1993; 14: 348–399.Google Scholar
  7. 7.
    Sap J, Munoz A, Damm K, Goldberg Y, Ghysdael J, Leutz A, Beug H, Vennstrom B. The c-erb A protein is a high affinity receptor for thyroid hormone. Nature 1986; 324: 635–640.PubMedCrossRefGoogle Scholar
  8. 8.
    Weinberger C, Thompson C, Ong E, Lebo R, Gruol D, Evans R. The c-erb gene encodes a thyroid hormone receptor. Nature 1986; 324: 641–646.PubMedCrossRefGoogle Scholar
  9. 9.
    Evans R. The steroid and thyroid hormone receptor superfamily. Science 1988; 240: 889–895.PubMedCrossRefGoogle Scholar
  10. 10.
    Chin W. Nuclear thyroid hormone receptors. In: Parker MG, ed. Nuclear hormone receptors. London, Academic, 1991, pp. 79–102.Google Scholar
  11. 11.
    Forman B, Samuels H. Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model. Mol Endocrinol 1990; 4: 1293–1301.PubMedCrossRefGoogle Scholar
  12. 12.
    Wagner R, Apriletti J, McGrath M, West B, Baxter J, Fletterick R. A structural role for hormone in the thyroid hormone receptor. Nature 1995; 378: 690–697.PubMedCrossRefGoogle Scholar
  13. 13.
    Hodin R, Lazar M, Wintman B, Darling D, Koenig R, Larsen P, Moore D, Chin W. Identification of a novel thyroid hormone receptor that is pituitary specific. Science 1989; 244: 76–79.PubMedCrossRefGoogle Scholar
  14. 14.
    Katz D, Reginato M, Lazar M. Functional regulation of thyroid hormone receptor variant TR alpha 2 by phosphorylation. Mol Cell Biol 1995; 15: 2341–2348.PubMedGoogle Scholar
  15. 15.
    Saatcioglu F, Deng T, Karin M. A novel cis element mediating ligand-independent activation by c-erbA: implications for hormonal regulation. Cell 1993; 75: 1095–1105.PubMedCrossRefGoogle Scholar
  16. 16.
    Farsetti A, Desvergne B, Hallenbeck P, Robbins J, Nikodem V. Characterization of myelin basic protein thyroid hormone response element and its function in the context of native and heterologous promoter. J Biol Chem 1992;267:15, 784–15, 788.Google Scholar
  17. 17.
    Lezoualc’h F, Hassan A, Giraud P, Loeffler J, Lee S, Demeneix B. Assignment of the beta-thyroid hormone receptor to 3,5,3 ’-triiodothyronine-dependent inhibition of transcription from thyrotropin-releasing hormone promoter in chick hypothalamic neurons. Mol Endocrinol 1992; 6: 1797–1804.PubMedCrossRefGoogle Scholar
  18. 18.
    Barettino D, VivancoRuiz M, Stunnenberg H. Characterization of the ligand-dependent trans-activation domain of thyroid hormone receptor. EMBO J 1994; 13: 3039–3049.PubMedGoogle Scholar
  19. 19.
    Nagpal S, Friant S, Nakshatri H, Chambon P. RARs and RXRs: Evidence for two autonomous transactivation functions (AF-1 and AF-2) and heterodimerization in vivo. EMBO J 1993; 12: 2349–2360.PubMedGoogle Scholar
  20. 20.
    Tone Y, Collingwood T, Adams M, Chatterjee V. Functional analysis of a transactivation domain in the thyroid hormone ß receptor. J Biol Chem 1994;269:31, 157–31, 161.Google Scholar
  21. 21.
    Cook C, Kakucska I, Lechan R, Koenig R. Expression of thyroid hormone receptor ß2 in rat hypothalamus. Endocrinology 1992; 130: 1077–1079.PubMedCrossRefGoogle Scholar
  22. 22.
    Bradley D, Towle H, Young W. Spatial and temporal expression of α -and β-thyroid hormone receptor mRNAs, including the β2-subtype, in the developing mammalian system. J Neurosci 1992; 12: 2288–2302.PubMedGoogle Scholar
  23. 23.
    Bradley D, Towle H, Young W. Alpha and beta thyroid hormone receptor (TR) gene expression during auditory neurogenesis: evidence for TR isoform-specific transcriptional regulation in vivo. Proc Natl Acad Sci USA 1994; 91: 439–443.PubMedCrossRefGoogle Scholar
  24. 24.
    Schwartz HL, Strait KA, Ling NC, Oppenheimer JH. Quantitation of rat tissue thyroid hormone binding receptor isoforms by immunoprecipitation of nuclear triiodothyronine binding capacity. J Biol Chem 1992;267:11, 794–11, 799.Google Scholar
  25. 25.
    Oppenheimer J, Schwartz H, Strait K. An integrated view of thyroid hormone actions in. In: B. Weintraub, ed. Molecular Endocrinology: Basic concepts and clinical correlations. Raven, New York, 1995, pp. 249–268.Google Scholar
  26. 26.
    Hodin R, Lazar M, Chin W. Differential and tissue-specific regulation of the multiple rat c-erbA mRNA species by thyroid hormone. J Clin Invest 1990; 85: 101–105.PubMedCrossRefGoogle Scholar
  27. 27.
    Brent G, Harney J, Chen Y, Warne R, Moore D, Larsen P. Mutations of the rat growth hormone promoter which increase and decrease response to thyroid hormone promoter which increase and decrease response to thyroid hormone define a consensus thyroid hormone response element. Mol Endocrinol 1989; 3: 1996–2004.PubMedCrossRefGoogle Scholar
  28. 28.
    Chin W, Carr F, Burnside J, Darling DS. Thyroid hormone regulation of thyrotropin gene expression. Rec Prog in Horm Res 1993; 48: 393–414.Google Scholar
  29. 29.
    Naar A, Boutin J, Lipkin S, Yu V, Holloway J, Glass C, Rosenfeld M. The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors. Cell 1991; 65: 1255–1266.CrossRefGoogle Scholar
  30. 30.
    Umesono K, Marakami K, Thompson C, Evans R. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell 1991; 65: 1255–1266.PubMedCrossRefGoogle Scholar
  31. 31.
    Forman B, Casanova J, Raaka B, Ghysdael J, Samuels H. Half-site spacing and orientation determines whether thyroid hormone and retinoic acid receptor and related factors bind to DNA response elements as monomers, homodimers, or heterodimers. Mol Endocrinol 1992; 6: 29–442.CrossRefGoogle Scholar
  32. 32.
    Baniahmad A, Steiner A, Kohne A, Renkawitz R. Modular structure of a chicken lysozyme silencer: Involvement of an unusual thyroid hormone receptor. Cell 1990; 61: 505–514.Google Scholar
  33. 33.
    Glass C, Holloway J, Devary O, Rosenfeld M. The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence in thyroid hormone and estrogen response elements. Cell 1988; 54: 313–323.PubMedCrossRefGoogle Scholar
  34. 34.
    Mader S, Leroy P, Chen J, Chambon P. Multiple parameters control the selectivity of nuclear receptors for their response elements. Selectivity and promiscuity in response element recognition by retinoic acid receptors and retinoid X receptors. J Biol Chem 1993; 268: 591–600.PubMedGoogle Scholar
  35. 35.
    Force W, Tillman J, Sprung C, Spindler S. Homodimer and heterodimer DNA binding and transcriptional responsiveness to triiodothyronine (T3) and 9-cis-retinoic acid are determined by the number and order of high affinity half-sites in a T3 response element. J Biol Chem 1994; 269: 8863–8871.PubMedGoogle Scholar
  36. 36.
    Katz R, Koenig R. Specificity and mechanism of thyroid hormone induction from an octamer response element. J Biol Chem 1994;269:18, 915–18, 920.Google Scholar
  37. 37.
    Katz R, Koenig R. Nucleotide substitutions differentially affect direct repeat and palindromic thyroid hormone response elements. J Biol Chem 1994; 269: 9500–9505.PubMedGoogle Scholar
  38. 38.
    Katz R, Koenig R. Nonbiased identification of DNA sequences that bind thyroid hormone receptor alpha 1 with high affinity. J Biol Chem 1993;268:19, 392–19, 397.Google Scholar
  39. 39.
    Suen CS, Yen P, Chin W. In vitro transcriptional studies of the roles of the roles of the thyroid hormone (T3) response elements and minimal promoters in T3-stimulated gene transcription. J Biol Chem 1994; 269: 1314–1322.PubMedGoogle Scholar
  40. 40.
    Darling DS, Carter RL, Yen PM, Welborn JM, Chin WW, Umeda PK. Different dimerization activities of a and)3 thyroid hormone receptor isoforms. J Biol Chem 1993;268:10, 221–10, 227.Google Scholar
  41. 41.
    Murray M, Towle H. Identification of nuclear factors that enhance binding of the thyroid hormone receptor to a thyroid hormone response element. Mol Endocrinol 1989; 3: 1434–1442.PubMedCrossRefGoogle Scholar
  42. 42.
    Burnside J, Darling D, Chin W. A nuclear factor that enhances binding of thyroid hormone receptors to thyroid hormone response elements. J Biol Chem 1990; 265: 2500–2504.PubMedGoogle Scholar
  43. 43.
    Darling D, Beebe J, Burnside J, Winslow E, Chin W. 3,5,3 ’-Triiodothyronine (T3) receptor auxiliary protein (TRAP) binds DNA and forms heterodimers with the T3 receptor. Mol Endocrinol 1991; 5: 73–84.PubMedCrossRefGoogle Scholar
  44. 44.
    Mangelsdorf D, Ong E, Dyck J, Evans R. Nuclear receptor that identifies a novel retinoic acid response pathway. Nature 1990; 345: 224–229.PubMedCrossRefGoogle Scholar
  45. 45.
    Yu V, Delsert C, Andersen B, Holloway J, Devary O, Naar A, Kim S, Boutin J, Glass C, Rosenfeld M. RXRß: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements. Cell 1991; 67: 1251–1266.PubMedCrossRefGoogle Scholar
  46. 46.
    Kliewer S, Umesono K, Mangelsdorf D, Evans R. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone, and vitamin D3 signalling. Nature 1992; 355: 446–449.PubMedCrossRefGoogle Scholar
  47. 47.
    Marks M, Hallenbeck P, Nagata T, Segars J, Appella E, Nikodem V, Ozato K. H-2RIIBP (RXRβ) heterodimerization provides a mechanism for combinatorial diversity in the regulation of retinoic acid and thyroid hormone responsive genes. EMBO J 1992; 11: 1419–1435.PubMedGoogle Scholar
  48. 48.
    Zhang X, Hoffman B, Tran PV, Graupner G, Pfahl M. Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors. Nature 1992; 355: 441–446.PubMedCrossRefGoogle Scholar
  49. 49.
    Leid M, Kastner P, Lyons R, Naksatri H, Saunders M, Zacharewski T, Chem J, Staub A, Gamier J-M, Mader S, Chambon P. Purification, cloning and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell 1992; 68: 377–395.PubMedCrossRefGoogle Scholar
  50. 50.
    Mangelsdorf D, Borgmeyer U, Heyman R, Zhou J, Ong E, Oro A, Kakizuka A, Evans R. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev 1992; 6: 329–344.PubMedCrossRefGoogle Scholar
  51. 51.
    Sugawara A, Yen P, Darling D, Chin W. Characterization and tissue expression of multiple triiodothyronine (T3,) receptor auxiliary proteins (TRAPs) and their relationship to the retinoid X receptors (RXRs). Endocrinology 1993; 133: 965–971.PubMedCrossRefGoogle Scholar
  52. 52.
    Berrodin T, Marks M, Ozato K, Linney E, Lazar M. Heterodimerization among thyroid hormone receptor, retinoic acid receptor, retinoid X receptor, chicken ovalbumin upstream promoter transcription factor, and an endogenous nuclear protein. Mol Endocrinol 1992; 6: 1468–1478.PubMedCrossRefGoogle Scholar
  53. 53.
    Heyman R, Mangelsdorf D, Dyk J, Stein R, Eichele G, Evans R, Thaller C. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 1992; 68: 397–440.PubMedCrossRefGoogle Scholar
  54. 54.
    Levin A, Sturzenbecker L, Kaxmer S, Bosakowski T, Huselton C, Allenby G, Speck L, Kratzeisen C, Rosenberger M, Lovey A, Grippo J. 9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR«. Nature 1992; 355: 359–361.PubMedCrossRefGoogle Scholar
  55. 55.
    Perlmann T, Rangarajan P, Umesono K, Evans R. Determinants for selective RAR and TR recognition of direct repeat HREs. Genes Dev 1993; 7: 1411–1422.PubMedCrossRefGoogle Scholar
  56. 56.
    Kurokawa R, Yu V, Naar A, Kyakumoto S, Han Z, Silverman S, Rosenfeld M, Glass C. Differential orientations of the DNA-binding domain and carboxy-terminal dimerization interface regulate binding site selection by nuclear receptor heterodimers. Gene Dev 1993; 7: 1423–1435.PubMedCrossRefGoogle Scholar
  57. 57.
    Yen P, Ikeda M, Wilcox E, Brubaker J, Spanjaard R, Sugawara A, Chin W. Half-site arrangement of hybrid glucocorticoid and thyroid hormone response elements specifies thyroid hormone receptor complex binding to DNA and transcriptional activity. J Biol Chem 1994;269: 12, 704–12, 709.Google Scholar
  58. 58.
    Hallenbeck P, Phyillaier M, Nikodem V. Divergent effects of 9-cis retinoic acid receptor on positive and negative thyroid hormone receptor-dependent gene expression. J Biol Chem 1993; 268: 3825–3828.PubMedGoogle Scholar
  59. 59.
    Rosen E, O’Donnell A, Koenig R. Ligand-dependent synergy of thyroid hormone and retinoid X receptors. J Biol Chem 1992;267:22, 010–22, 013.Google Scholar
  60. 60.
    Hall B, Smit-McBride Z, Privalsky M. Reconstitution of retinoid X receptor function and combinatorial regulation of other nuclear hormone receptors in yeast Saccharomyces cerevisiae. Proc Natl Acad Sci USA 1993; 90: 6929–6933.PubMedCrossRefGoogle Scholar
  61. 61.
    Lee I, Driggers P, Medin J, Nikodem V, Ozato K. Recombinant thyroid hormone receptor and retinoid X receptor stimulate ligand-dependent transcription in vitro. Proc Natl Acad Sci USA 1994; 91: 1647–1651.PubMedCrossRefGoogle Scholar
  62. 62.
    Bogazzi F, Hudson L, Nikodem V. A novel heterodimerization partner for thyroid hormone receptor. Peroxisome proliferator-activated receptor. J Biol Chem 1994;269:11, 683–11, 686.Google Scholar
  63. 63.
    Lu X, Eberhardt N, Pfahl M. DNA bending by retinoid X receptor-containing retinoid and thyroid hormone receptor complexes. Mol Cell Biol 1993; 13: 6509–6519.PubMedGoogle Scholar
  64. 64.
    Ikeda M, Wilcox E, Chin W. Different DNA elements can modulate the conformation of the thyroid hormone receptor heterodimer and its transcriptional activity. J Biol Chem 1996;271: 23, 076–23, 104.Google Scholar
  65. 65.
    Refetoff S, Weiss R, Usala S. The syndromes of resistance to thyroid hormone. Endocr Rev 1993; 14: 348–399.PubMedGoogle Scholar
  66. 66.
    Yen P, Sugawara A, Refetoff S, Chin W. New insights on the mechanism(s) of the dominant negative effect of mutant thyroid hormone receptor in generalized resistance to thyroid hormone. J Clin Invest 1992; 90: 1825–1831.PubMedCrossRefGoogle Scholar
  67. 67.
    Toney J, Wu L, Summerfield A, Sanyal G, Forman B, Zhu J, Samuels H. Conformational changes in chicken thyroid hormone receptor alpha I induced by binding to ligand or to DNA. Biochemistry 1993; 32: 26.Google Scholar
  68. 68.
    Leng X, Tsai S, O’Malley B, Tsai M. Ligand-dependent conformational changes in thyroid hormone and retinoic acid receptors are potentially enhanced by heterodimerization with retinoic X receptor. J Steroid Biochem Mol Biol 1993; 46: 643–661.PubMedCrossRefGoogle Scholar
  69. 69.
    Yen P, Brubaker J, Apriletti J, Baxter J, Chin W. Roles of T3 and DNA-binding on thyroid hormone receptor complex formation. Endocrinology 1994; 134: 1075–1081.PubMedCrossRefGoogle Scholar
  70. 70.
    Yen P, Darling D, Carter R, Forgione M, Umeda P, Chin W. Triiodothyronine (T3) decreases DNA-binding of receptor homodimers but not receptor-auxiliary protein heterodimers. J Biol Chem 1992; 267: 3565–3568.PubMedGoogle Scholar
  71. 71.
    Yen P, Sugawara A, Chin W. Triiodothyronine (T3) differentially affects T3-receptor/retinoic acid receptor and T3-receptor/retinoid X receptor heterodimer binding to DNA. J Biol Chem 1992;267:23, 248–23, 252.Google Scholar
  72. 72.
    Ribeiro R, Kushman P, Apriletti J, West B, Baxter J. Thyroid hormone alters in vitro DNA binding of monomers and dimers of thyroid hormone receptors. Mol Endocrinol 1992; 6: 1142–1152.PubMedCrossRefGoogle Scholar
  73. 73.
    Miyamoto T, Suzuki S, DeGroot L. High affinity and specificity of dimeric binding of thyroid hormone receptors to DNA and their ligand dependent dissociation. Mol Endocrinol 1993; 7: 224–231.PubMedCrossRefGoogle Scholar
  74. 74.
    Andersson M, Nordstrom K, Demezuk S, Harbers M, Vennstrom B. Thyroid hormone alters the DNA binding properties of chicken thyroid hormone receptors a and ß. Nucl Acids Res 1992; 20: 4803–4870.PubMedCrossRefGoogle Scholar
  75. 75.
    Power R, Main S, Codina J, Coneely O, O’Malley B. Dopaminergic and ligand-independent activation of steroid hormone receptors. Science 1991; 254: 1636–1639.PubMedCrossRefGoogle Scholar
  76. 76.
    Goldberg Y, Glineur C, Resquiere JC, Ricouart A, Sap J, Vennstrom 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; 7: 2425–2433.Google Scholar
  77. 77.
    Swierczynski J, Mitchell D, Reinhold D, Salati L, Stapleton S, Klautky S, Struve A, Goodridge A. Triiodothyronine-induced accumulations of malic enzyme, fatty acid synthase, acetyl coenzyme A carboxylase and their mRNAs are blocked by protein kinase inhibitors. Transcription is the affected step. J Biol Chem 1991;266:17, 459–17, 466.Google Scholar
  78. 78.
    Jones K, Brubaker J, Chin W. Evidence that phosphorylation events participate in thyroid hormone action. Endocrinology 1994; 134: 543–548.PubMedCrossRefGoogle Scholar
  79. 79.
    Sugawara A, Yen P, Apriletti J, Ribeiro R, Sacks D, Baxter J, Chin W. Phosphorylation selectively increases triiodothyronine (T3)-receptor homodimer binding to DNA. J Biol Chem 1994; 269: 433–437.PubMedGoogle Scholar
  80. 80.
    Bhat M, Ashizawa K, Cheng S. Phosphorylation enhances the target gene sequence-dependent dimerization of thyroid hormone receptor with retinoid X receptor. Proc Natl Acad Sci USA 1994; 91: 7927–7931.PubMedCrossRefGoogle Scholar
  81. 81.
    Buratowski S. The basics of basal transcription by RNA polymerase II. Cell 1994; 77: 1–3.PubMedCrossRefGoogle Scholar
  82. 82.
    Dynlacht B, Hoey T, Tjian R. Isolation of coactivators associated with the TATA-binding protein that mediate transcriptional activation. Cell 1991; 66: 563–576.PubMedCrossRefGoogle Scholar
  83. 83.
    Gill G, Tjian R. Eukaryotic coactivators associated with the TATA box binding protein. Curr Op Gen Dev 1992; 2: 236–242.CrossRefGoogle Scholar
  84. 84.
    Berger S, Cress W, Cress A, Triezenberg S, Guarente L. Selective inhibition of activated but not basal transcription by the acidic activation domain of VP16: evidence for transcriptional adaptors. Cell 1990; 61: 1199–1208.PubMedCrossRefGoogle Scholar
  85. 85.
    Hoey T, Weinzierl R, Gill G, Chen J, Dynlacht B, Tjian R. Molecular cloning and functional analysis of Drosophila TAF110 reveal properties expected of coactivators. Cell 1993; 72: 247–260.PubMedCrossRefGoogle Scholar
  86. 86.
    Goodrich J, Hoey T, Thur C, Admon A, Tjian R. Drosophila TAFII40 interacts with both a VP16 activation domain and the basal transcription factor. Cell 1993; 75: 513–530.CrossRefGoogle Scholar
  87. 87.
    Roberts S, Ha I, Maldonado E, Reinberg D, Green M. Interaction between an acidic activator and transcription factor TFIIB is required for transcriptional activation. Nature 1993; 363: 741–744.PubMedCrossRefGoogle Scholar
  88. 88.
    Tjian R, Maniatis T. Transcriptional activation: a complex puzzle with few easy pieces. Cell 1994; 77: 5–8.PubMedCrossRefGoogle Scholar
  89. 89.
    Kim Y, Bjorklund S, Li Y, Sayre M, Kornberg R. A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Cell 1994; 77: 599–608.PubMedCrossRefGoogle Scholar
  90. 90.
    Inostroza J, Mermelstein F, Ha I, Lane W, Reinberg D. Dr1-a TATA binding protein-associated phosphoprotein and inhibitor of class II gene transcription. Cell 1992; 70: 477–489.PubMedCrossRefGoogle Scholar
  91. 91.
    Brent G, Dunn M, Harney J, Gulick T, Larsen P, Moore D. Thyroid hormone aporeceptor represses T3-inducible promoters and blocks activity of the retinoic acid receptor. New Biol 1989; 1: 329–336.PubMedGoogle Scholar
  92. 92.
    Baniahmad A, Tsai S, O’Malley B, Tsai M. Kindred S thyroid hormone receptor is an active and constitutive silencer and a repressor for thyroid hormone and retinoic acid responses. Proc Natl Acad Sci USA 1992;89:10, 633–10, 637.Google Scholar
  93. 93.
    Zhang X, Wills K, Graupner G, Tzukerman M, Hermann T, Pfahl M. Ligand-binding domain of thyroid hormone receptors modulates DNA binding and determines their bifunction roles. New Biol 1991; 3: 169–181.PubMedGoogle Scholar
  94. 94.
    Yen P, Wilcox E, Hayashi Y, Refetoff S, Chin W. Studies on the repression of basal transcription (silencing) by artificial and natural thyroid hormone receptor-ß mutants. Endocrinology 1995; 136: 2845–2851.PubMedCrossRefGoogle Scholar
  95. 95.
    Horlein A, Naar A, Heinzel T, Torchia J, Gloss B, Kurokawa R, Ryan A, Kamel Y, Soderstrom M, Glass C, Rosenfeld M. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear co-repressor. Nature 1995; 377: 397–404.PubMedCrossRefGoogle Scholar
  96. 96.
    Chen J, Evans R. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature 1995; 377: 454–457.PubMedCrossRefGoogle Scholar
  97. 97.
    Lee J, Ryan F, Swaffield J, Johnston S, Moore D. Interaction of thyroid-hormone receptor with a conserved transcriptional mediator. Nature 1995; 374: 91–94.PubMedCrossRefGoogle Scholar
  98. 98.
    Baniahmad A, Ha I, Reinberg D, Tsai M, Tsai S, O’Malley B. Interaction of human thyroid hormone receptor ß with transcription factor TFIIB may mediate target gene derepression and activation by thyroid hormone. Proc Natl Acad Sci USA 1993; 90: 8832–8836.PubMedCrossRefGoogle Scholar
  99. 99.
    Fondell J, Roy A, Roeder R. Unliganded thyroid hormone receptor inhibits formation of a functional preinitiation complex: implications for active repression. Genes Dev 1993; 7: 1400–1410.PubMedCrossRefGoogle Scholar
  100. 100.
    Suen C, Chin W. A potential transcriptional adaptor(s) may be required in thyroid hormone-stimulated gene transcription in vitro. Endocrinology 1995; 136: 277–683.CrossRefGoogle Scholar
  101. 101.
    Onate S, Tsai S, Tsai M, O’Malley B. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science 1995; 270: 1354–1357.PubMedCrossRefGoogle Scholar
  102. 102.
    Takeshita A, Yen P, Misiti S, Cardona G, Liu Y, Chin W. Molecular cloning and properties of a full-length putative thyroid hormone receptor coactivator. Endocrinology 1996; 137: 3594–3597.PubMedCrossRefGoogle Scholar
  103. 103.
    Chakravarti D, LaMorte V, Nelson M, Nakajima T, Schulman I, Juguilon H, Montminy M, Evans R. Role of CBP/P300 in nuclear receptor signalling. Nature 1996; 383: 99–102.PubMedCrossRefGoogle Scholar
  104. 104.
    Kamei Y, Xu L, Heinzel T, Torchia J, Kurokawa R, Gloss B, SC Lin RH, Rose D, Glass C, Rosenfeld M. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 1996; 85: 403–414.PubMedCrossRefGoogle Scholar
  105. 105.
    Halachmi S, Marden E, Martin G, MacKay H, Abbondanze C, Brown M. Estrogen receptor-associated proteins: possible mediators of hormone-induced transcription. Science 1994; 264: 1455–1458.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • William W. Chin
  • Paul M. Yen

There are no affiliations available

Personalised recommendations