Abstract
Thyroid hormone receptors (TRs) are capable of both activating and repressing transcription from genes bearing TR-binding elements (TREs). In general, TRs function as activators in the presence of thyroid hormone (T3) and repressors in the absence of T3 (1). The ability of TRs to regulate transcription has been linked to their ability to recruit distinct types of transcriptional coregulatory factors, termed coactivators and corepressors, to target gene promoters (2,3). Remarkably, yeast 2-hybrid and conventional expression library screens have identified numerous TR-binding coregulatory factors (reviewed in refs. 2 and 3). The best characterized TR coactivators include members the p160/SRC family (2-4). While the precise mechanism of action of the p160/ SRC proteins is still being defined, their ability to associate with histone acetyltransferases (HATs) such as the CREB-binding protein (CBP) and p300, and the presence of intrinsic HAT activity in some family members indicates a functional role in chromatin modification (2-4).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Lazar, M. A. (1993) Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr. Rev. 14, 184–193.
Glass, C. K. and Rosenfeld, M. G. (2000) The coregulator exchange in transcriptional functions of nuclear receptors. Genes & Dev. 14, 121–141.
McKenna, N. J., Lanz, R. B., and O’Malley, B. W. (1999) Nuclear recepto coregulators: cellular and molecular biology. Endocr. Rev. 20, 321–344.
Moras, D. and Gronemeyer, H. (1998) the nuclear receptor ligand-binding domain: structure and function. Curr. Opin. Cell Biol. 10, 384–391.
Fondell, J. D., Ge, H., and Roeder, R. G. (1996) Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proc. Natl. Acad. Sci. USA 93, 8329–8333.
Fondell, J. D., Guermah, M., Malik, S., and Roeder, R. G. (1999) Thyroid hormone receptor-associated proteins and general positive cofactors mediate thyroid hormone receptor function in the absence of the TATA box-binding protein-associated factors of TFIID. Proc. Natl. Acad. Sci. USA 96, 1959–1964.
Myers, L. C., Gustafsson, C. M., Bushnell, D. A., et al. (1998) The Med proteins of yeast and their function through the RNA polymerase II carboxy-terminal domain. Genes Dev. 12, 45–54.
Ito, M., Yuan, C.-X., Malik, S., et al. (1999) Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Mol. Cell 3, 361–370.
Rachez, C., Lemon, B.D., Suldan, Z., et al. (1999) Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 398, 824–828.
Ren, Y., Behre, E., Ren, Z., Zhang, J., Wang, Q., and Fondell, J. D. (2000) Specific structural motifs determine TRAP220 interactions with nuclear hormone receptors. Mol. Cell Biol. 20, 5433–5446.
Malik, S. and Roeder, R. G. (2000) Transcriptional regulation through mediatorlike coactivators in yeast and metazoan cells. Trends Biochem. Sci. 25, 277–283.
Chiang, C.-M. and Roeder, R. G. (1993) Expression and purification of general transcription factors by FLAG-tagging and peptide elution. Peptide Res. 6, 62–64.
Morgenstern, J. P. and Land, H. (1990) Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line. Nucl. Acids Res. 18, 3587–3596.
Danos, O. and Mulligan, R. C. (1988) Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc. Natl. Acad. Sci. USA 85, 6460–6464.
Sawadogo, M. and Roeder, R. G. (1985) Factors involved in specific transcription by human RNA polymerase II: analysis by a rapid and quantitative in vitro assay. Proc. Natl. Acad. Sci. USA 85, 6460–6464.
Fondell, J. D., Roy, A. L. and Roeder, R. G. (1993) Unliganded thyroid hormone receptor inhibits formation of a functional preinitiation complex: implications for active repression. Genes Dev. 7, 1400–1410.
Parker, B. A., and Stark, G. R. (1979) Regulation of simian virus 40 transcription: sensitive analysis of the RNA species present early in infections by virus or viral DNA. J. Virol. 31, 360–369.
Sharma, D. and Fondell, J. D. (2000) Temporal formation of distinct thyroid hormone receptor coactivator complexes in HeLa cells. Mol. Endocrinol. 14, 2001–2009.
Dignam, J. D. (1990) Preparation of extracts from higher eukaryotes. Methods Enzymol. 182, 194–202.
Zhang, J. and Fondell, J. D. (1999) Identification of mouse TRAP100: a transcriptional coregulatory factor for thyroid hormone and vitamin D receptors. Mol. Endocrinol. 13, 947–955.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Humana Press Inc.
About this protocol
Cite this protocol
Fondell, J.D. (2002). Gene Activation by Thyroid Hormone Receptor In Vitro and Purification of the TRAP Coactivator Complex. In: Baniahmad, A. (eds) Thyroid Hormone Receptors. Methods in Molecular Biology, vol 202. Humana Press. https://doi.org/10.1385/1-59259-174-4:195
Download citation
DOI: https://doi.org/10.1385/1-59259-174-4:195
Publisher Name: Humana Press
Print ISBN: 978-0-89603-995-7
Online ISBN: 978-1-59259-174-9
eBook Packages: Springer Protocols