The coregulator exchange in transcriptional functions of nuclear receptors.

By Christopher K. Glass, Michael G. Rosenfeld. Genes & Development, 2000

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Nuclear receptors (NR) comprise a family of transcription factors that regulate gene expression in a liganddependent manner. Members of the NR superfamily include receptors for steroid hormones, such as estrogens (ER) and glucocorticoids (GR), receptors for nonsteroidal ligands, such as thyroid hormones (TR) and retinoic acid (RAR), as well as receptors that bind diverse products of lipid metabolism, such as fatty acids and prostaglandins (for review, see Beato et al. 1995; Chambon 1995; Mangelsdorf and Evans 1995). The NR superfamily also includes a large number of so-called orphan receptors for which regulatory ligands have not been identified (Mangelsdorf and Evans 1995). Although many orphan receptors are likely to be regulated by small-molecular-weight ligands, other mechanisms of regulation, such as phosphorylation (Hammer et al. 1999; Tremblay et al. 1999) have also proven to be of importance. Remarkably, the sequence of the Caenorhabditis elegans genome has revealed the presence of >200 members of the NR family, suggesting a critical role of these proteins in environmental adaptation (Sluder et al. 1999). Although mammalian genomes are unlikely to contain such a large complement of these factors, >24 distinct classes of NR have been identified in humans, and these factors exert diverse roles in the regulation of growth, development, and homeostasis. Based on their importance in biology and medicine, as well as the relatively simple mechanism of regulation, NR represent one of the most intensively studied and best-understood classes of transcription factors at the molecular level. Members of the NR family regulate transcription by several mechanisms (Fig. 1). Nuclear receptors can activate or repress target genes by binding directly to DNA response elements as homoor heterodimers or by binding to other classes of DNA-bound transcription factors. A subset of NRs, including TR and RAR, can actively repress target genes in the presence or absence of ligand binding, and many NR have been demonstrated to inhibit transcription in a ligand-dependent manner by antagonizing the transcriptional activities of other classes of transcription factors. These activities have been linked to interactions with general classes of molecules that appear to serve coactivator or corepressor function. In this review, we will discuss recent progress concerning the molecular mechanisms by which NR cofactor interactions serve to activate or repress transcription.

Subfields: Cellular and Molecular Neuroscience, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e16d88ae17b0551bf719f30e2c0006cad1cc5471

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Citations in the corpus

Androgen receptor (AR) coregulators: an overview. (2002, background): “It has been postulated that coregulators exist in partially assembled holocomplexes in the nucleus, similar to the RNA pol II holocomplex (29, 137).”
Atherosclerosis The Road Ahead (2001, background): “…and should be useful in selecting candidates that have these that appear to integrate the activities of nuclear recep- properties for testing in vivo. tors with other transcription factors in a promoter-spe- LXRs have more recently emerged as transcription cific manner (Glass and Rosenfeld, 2000).”
The SMRT and N-CoR Corepressors Are Activating Cofactors for Histone Deacetylase 3 (2001, background): “Gal4SMRT DAD mutants W432A, F440A, F451A, I454A, L458A, V463A, and Y470A were produced using the corresponding mutagenic oligonucleotides and the QuickChange site-directed mutagenesis kit (Stratagene).”
The aryl hydrocarbon receptor complex and the control of gene expression. (2008, background): “The classic model of NR activation by ligand suggests that ligand facilitates an exchange of NCoR/ SMRT/Sin3/HDAC corepressor complexes for coactivator complexes with ATP-dependent chromatin remodeling and histone acetyl-transferase activities.(197,198) It has been suggested that this happens only i”
International Union of Pharmacology. LXI. Peroxisome Proliferator-Activated Receptors (2006, background): “Often, the repressive effects depend on the recruitment of histone deacetylases, but sometimes direct contacts with the basal transcription machinery are also possible (Glass and Rosenfeld, 2000; McKenna and O’Malley, 2002; Hebbar and Archer, 2003).”