Thyroid hormone dependent gene expression

Ghulam Zahara Jahangir, Faiza Saleem, Shagufta Naz, Neelma Munir, Rukhama Haq, Aleena Sumrin


The presented work is destined to review the advances that had been made to study the role of thyroid hormone and thyroid hormone nuclear receptors in regulating the gene expression. Triiodothyronine (T3) and tetraiodothyronine (thyroxine or T4) are most important thyroid hormones. The thyroid hormones bind to their specific nuclear hormone receptors, as ligand, and play important role in gene expression and transcriptional gene regulation in human and higher animals. Thyroid hormone receptors form heterodimers by making combination with retinoid X receptors. The capability of heterodimerization of thyroid hormones generates novel complexes which allow altered specificity and higher affinity for DNA-receptor binding. Thyroid hormone receptors work as ligand activated transcription factor and play with transcriptional gene expression process. The consensus structural features of thyroid hormone receptors are N-terminal regulatory domain that contains activation function, the domain for strong gene expression and the domain for binding to DNA. The structures for individual domains have been extensively and reviewed through several latest and successful techniques.  

Full Text:



Beato M (1993) Gene regulation by steroid hormones. Gene Expression: Springer. pp. 43-75.

Wolff E, Wolff J. The mechanism of action of the thyroid hormones. The Thyroid Gland, (1964); 1237-282.

Samuels H, Forman B, Horowitz Z, Ye Z. Regulation of gene expression by thyroid hormone. Journal of Clinical Investigation, (1988); 81(4): 957.

Aranda A, Pascual A. Nuclear hormone receptors and gene expression. Physiological Reviews, (2001); 81(3): 1269-1304.

Brent GA. The molecular basis of thyroid hormone action. New England Journal of Medicine, (1994); 331(13): 847-853.

Mullur R, Liu Y-Y, Brent GA. Thyroid hormone regulation of metabolism. Physiological Reviews, (2014); 94(2): 355-382.

Zhang J, Lazar MA. The mechanism of action of thyroid hormones. Annual Review of Physiology, (2000); 62(1): 439-466.

Robinson-Rechavi M, Garcia HE, Laudet V. The nuclear receptor superfamily. Journal of Cell Science, (2003); 116(4): 585-586.

Glass CK. Differential Recognition of Target Genes by Nuclear Receptor Monomers, Dimers, and Heterodimers*. Endocrine Reviews, (1994); 15(3): 391-407.

Forman BM, Umesono K, Chen J, Evans RM. Unique response pathways are established by allosteric interactions among nuclear hormone receptors. Cell, (1995); 81(4): 541-550.

Kumar R, Thompson EB. The structure of the nuclear hormone receptors. Steroids, (1999); 64(5): 310-319.

Wärnmark A, Treuter E, Wright AP, Gustafsson J-A. Activation functions 1 and 2 of nuclear receptors: molecular strategies for transcriptional activation. Molecular endocrinology, (2003); 17(10): 1901-1909.

Klinge CM. Estrogen receptor interaction with co-activators and co-repressors☆. Steroids, (2000); 65(5): 227-251.

Weatherman RV, Fletterick RJ, Scanlan TS. Nuclear-receptor ligands and ligand-binding domains. Annual review of biochemistry, (1999); 68(1): 559-581.

Roemer SC, Donham DC, Sherman L, Pon VH, Edwards DP, et al. Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements. Molecular Endocrinology, (2006); 20(12): 3042-3052.

Valadares NF, Salum LB, Polikarpov I, Andricopulo AD, Garratt RC. Role of halogen bonds in thyroid hormone receptor selectivity: pharmacophore-based 3D-QSSR studies. Journal of Chemical Information and Modeling, (2009); 49(11): 2606-2616.

Jin L, Martynowski D, Zheng S, Wada T, Xie W, et al. Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORγ. Molecular Endocrinology, (2010); 24(5): 923-929.

Dasgupta S, Lonard DM, O’Malley BW. Receptor Coactivators: Master Regulators of Human Health and Disease. Annual Review of Medicine, (2014); 65: 279.

Everett LJ, Lazar MA. Cell‐specific integration of nuclear receptor function at the genome. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, (2013); 5(5): 615-629.

Lu C, Thompson CB. Metabolic regulation of epigenetics. Cell Metabolism, (2012); 16(1): 9-17.

Beato M, Herrlich P, Schütz G. Steroid hormone receptors: many actors in search of a plot. Cell, (1995); 83(6): 851-857.

Umesono K, Giguere V, Glass CK, Rosenfeld MG, Evans RM. Retinoic acid and thyroid hormone induce gene expression through a common responsive element. Nature, (1988); 336(6196): 262-5.

Ribeiro R, Kushner PJ, Apriletti JW, West BL, Baxter JD. Thyroid hormone alters in vitro DNA binding of monomers and dimers of thyroid hormone receptors. Molecular Endocrinology, (1992); 6(7): 1142-1152.

Araki O, Ying H, Zhu X, Willingham M, Cheng S. Distinct dysregulation of lipid metabolism by unliganded thyroid hormone receptor isoforms. Molecular Endocrinology, (2009); 23(3): 308-315.

Mottis A, Mouchiroud L, Auwerx J. Emerging roles of the corepressors NCoR1 and SMRT in homeostasis. Genes & development, (2013); 27(8): 819-835.

Hsia EY, Goodson ML, Zou JX, Privalsky ML, Chen H-W. Nuclear receptor coregulators as a new paradigm for therapeutic targeting. Advanced Drug Delivery Reviews, (2010); 62(13): 1227-1237.

Belandia B, Latasa MJ, Villa A, Pascual A. Thyroid hormone negatively regulates the transcriptional activity of the β-amyloid precursor protein gene. Journal of Biological Chemistry, (1998); 273(46): 30366-30371.

Pérez-Juste G, Garcı́a-Silva S, Aranda A. An element in the region responsible for premature termination of transcription mediates repression of c-myc gene expression by thyroid hormone in neuroblastoma cells. Journal of Biological Chemistry, (2000); 275(2): 1307-1314.

Saatcioglu F, Deng T, Karin M. A novel cis element mediating ligand-independent activation by c-ErbA: implications for hormonal regulation. Cell, (1993); 75(6): 1095-1105.

Bigler J, Eisenman RN. Novel location and function of a thyroid hormone response element. The EMBO journal, (1995); 14(22): 5710.

Baniahmad A, Köhne A, Renkawitz R. A transferable silencing domain is present in the thyroid hormone receptor, in the v-erbA oncogene product and in the retinoic acid receptor. The EMBO Journal, (1992); 11(3): 1015.


  • There are currently no refbacks.