This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Harding, H. P.
Right arrow Articles by Lazar, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harding, H. P.
Right arrow Articles by Lazar, M. A.

 Previous Article  |  Next Article 

Mol. Cell. Biol., Sep 1995, 4791-4802, Vol 15, No. 9
Copyright © 1995, American Society for Microbiology

The monomer-binding orphan receptor Rev-Erb represses transcription as a dimer on a novel direct repeat [published erratum appears in Mol Cell Biol 1995 Nov;15(11):6479]

HP Harding and MA Lazar
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.

Rev-Erb is an orphan nuclear receptor which binds as a monomer to the thyroid/retinoic acid receptor half-site AGGTCA flanked 5' by an A/T- rich sequence, referred to here as a Rev monomer site. Fusion of Rev- Erb to the DNA binding domain of yeast GAL4 strongly repressed basal transcription of a GAL4-luciferase reporter gene as a result of the presence of a C-terminal domain containing both the hinge and heptad repeat regions. Nevertheless, wild-type Rev-Erb did not repress basal transcription from the Rev monomer binding site. Therefore, a DNA binding site selection strategy was devised to test the hypothesis that Rev-Erb may function on a different site as a dimer. This approach identified sequences containing two Rev monomer sites arranged as direct repeats with the AGGTCA motifs separated by 2 bp (Rev-DR2). Remarkably, Rev-Erb bound as a homodimer to Rev-DR2 but not to other direct repeats or to a standard DR2 sequence. The DNA binding domain contained all of the determinants for Rev-DR2-specific homodimerization. Rev-Erb bound cooperatively as a homodimer to Rev- DR2, and this interaction was 5 to 10 times more stable than Rev-Erb monomer binding to the Rev monomer site. Functionally, Rev-Erb markedly repressed the basal activity of a variety of promoters with a strong Rev-DR2 specificity. The C terminus was required for this repression, consistent with the GAL4 results. However, the Rev-DR2 specificity did not require the C terminus in vivo, since fusion of C-terminally truncated Rev-Erb to a heterologous transactivation domain created a transcriptional activator specific for Rev-DR2. In addition to idealized Rev-DR2 sites, Rev-Erb also repressed basal as well as retinoic acid-induced transcription from a naturally occurring Rev-DR2 in the CRBPI gene. Thus, although Rev-Erb is distinguished from other thyroid/steroid receptor superfamily members by its ability to bind DNA as a monomer, it functions as a homodimer to repress transcription of genes containing a novel DR2 element.


This article has been cited by other articles:

  • Wu, N., Yin, L., Hanniman, E. A., Joshi, S., Lazar, M. A. (2009). Negative feedback maintenance of heme homeostasis by its receptor, Rev-erb{alpha}. Genes Dev. 23: 2201-2209 [Abstract] [Full Text]  
  • Rambaud, J., Triqueneaux, G., Masse, I., Staels, B., Laudet, V., Benoit, G. (2009). Rev-erb{alpha}2 mRNA Encodes a Stable Protein with a Potential Role in Circadian Clock Regulation. Mol. Endocrinol. 23: 630-639 [Abstract] [Full Text]  
  • Hummasti, S., Tontonoz, P. (2008). Adopting New Orphans into the Family of Metabolic Regulators. Mol. Endocrinol. 22: 1743-1753 [Abstract] [Full Text]  
  • Fontaine, C., Rigamonti, E., Pourcet, B., Duez, H., Duhem, C., Fruchart, J.-C., Chinetti-Gbaguidi, G., Staels, B. (2008). The Nuclear Receptor Rev-erb{alpha} Is a Liver X Receptor (LXR) Target Gene Driving a Negative Feedback Loop on Select LXR-Induced Pathways in Human Macrophages. Mol. Endocrinol. 22: 1797-1811 [Abstract] [Full Text]  
  • Duez, H., Staels, B. (2008). The nuclear receptors Rev-erbs and RORs integrate circadian rhythms and metabolism. Diabetes and Vascular Disease Research 5: 82-88 [Abstract]  
  • Wang, J., Lazar, M. A. (2008). Bifunctional Role of Rev-erb{alpha} in Adipocyte Differentiation. Mol. Cell. Biol. 28: 2213-2220 [Abstract] [Full Text]  
  • Kakizawa, T., Nishio, S.-i., Triqueneaux, G., Bertrand, S., Rambaud, J., Laudet, V. (2007). Two differentially active alternative promoters control the expression of the zebrafish orphan nuclear receptor gene Rev-erb{alpha}. J Mol Endocrinol 38: 555-568 [Abstract] [Full Text]  
  • Germain, P., Staels, B., Dacquet, C., Spedding, M., Laudet, V. (2006). Overview of Nomenclature of Nuclear Receptors. Pharmacol. Rev. 58: 685-704 [Abstract] [Full Text]  
  • Benoit, G., Cooney, A., Giguere, V., Ingraham, H., Lazar, M., Muscat, G., Perlmann, T., Renaud, J.-P., Schwabe, J., Sladek, F., Tsai, M.-J., Laudet, V. (2006). International Union of Pharmacology. LXVI. Orphan Nuclear Receptors. Pharmacol. Rev. 58: 798-836 [Abstract] [Full Text]  
  • Anzulovich, A., Mir, A., Brewer, M., Ferreyra, G., Vinson, C., Baler, R. (2006). Elovl3: a model gene to dissect homeostatic links between the circadian clock and nutritional status. J. Lipid Res. 47: 2690-2700 [Abstract] [Full Text]  
  • Wang, J., Yin, L., Lazar, M. A. (2006). The Orphan Nuclear Receptor Rev-erb{alpha} Regulates Circadian Expression of Plasminogen Activator Inhibitor Type 1. J. Biol. Chem. 281: 33842-33848 [Abstract] [Full Text]  
  • Yin, L., Lazar, M. A. (2005). The Orphan Nuclear Receptor Rev-erb{alpha} Recruits the N-CoR/Histone Deacetylase 3 Corepressor to Regulate the Circadian Bmal1 Gene. Mol. Endocrinol. 19: 1452-1459 [Abstract] [Full Text]  
  • Triqueneaux, G., Thenot, S., Kakizawa, T., Antoch, M. P, Safi, R., Takahashi, J. S, Delaunay, F., Laudet, V. (2004). The orphan receptor Rev-erb{alpha} gene is a target of the circadian clock pacemaker. J Mol Endocrinol 33: 585-608 [Abstract] [Full Text]  
  • Cheng, H., Khanna, H., Oh, E. C.T., Hicks, D., Mitton, K. P., Swaroop, A. (2004). Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors. Hum Mol Genet 13: 1563-1575 [Abstract] [Full Text]  
  • Ishizuka, T., Lazar, M. A. (2003). The N-CoR/Histone Deacetylase 3 Complex Is Required for Repression by Thyroid Hormone Receptor. Mol. Cell. Biol. 23: 5122-5131 [Abstract] [Full Text]  
  • Raspe, E., Mautino, G., Duval, C., Fontaine, C., Duez, H., Barbier, O., Monte, D., Fruchart, J., Fruchart, J.-C., Staels, B. (2002). Transcriptional Regulation of Human Rev-erbalpha Gene Expression by the Orphan Nuclear Receptor Retinoic Acid-related Orphan Receptor alpha. J. Biol. Chem. 277: 49275-49281 [Abstract] [Full Text]  
  • Raspe, E., Duez, H., Mansen, A., Fontaine, C., Fievet, C., Fruchart, J.-C., Vennstrom, B., Staels, B. (2002). Identification of Rev-erb{alpha} as a physiological repressor of apoC-III gene transcription. J. Lipid Res. 43: 2172-2179 [Abstract] [Full Text]  
  • Swevers, L., Ito, K., Iatrou, K. (2002). The BmE75 Nuclear Receptors Function as Dominant Repressors of the Nuclear Receptor BmHR3A. J. Biol. Chem. 277: 41637-41644 [Abstract] [Full Text]  
  • Delerive, P., Chin, W. W., Suen, C. S. (2002). Identification of Reverbalpha as a Novel RORalpha Target Gene. J. Biol. Chem. 277: 35013-35018 [Abstract] [Full Text]  
  • Coste, H., Rodriguez, J. C. (2002). Orphan Nuclear Hormone Receptor Rev-erbalpha Regulates the Human Apolipoprotein CIII Promoter. J. Biol. Chem. 277: 27120-27129 [Abstract] [Full Text]  
  • Yen, P. M. (2001). Physiological and Molecular Basis of Thyroid Hormone Action. Physiol. Rev. 81: 1097-1142 [Abstract] [Full Text]  
  • Aranda, A., Pascual, A. (2001). Nuclear Hormone Receptors and Gene Expression. Physiol. Rev. 81: 1269-1304 [Abstract] [Full Text]  
  • Torra, I. P., Tsibulsky, V., Delaunay, F., Saladin, R., Laudet, V., Fruchart, J.-C., Kosykh, V., Staels, B. (2000). Circadian and Glucocorticoid Regulation of Rev-erb{alpha} Expression in Liver. Endocrinology 141: 3799-3806 [Abstract] [Full Text]  
  • Renaud, J.-P., Harris, J. M., Downes, M., Burke, L. J., Muscat, G. E .O. (2000). Structure-Function Analysis of the Rev-erbA and RVR Ligand-Binding Domains Reveals a Large Hydrophobic Surface That Mediates Corepressor Binding and a Ligand Cavity Occupied by Side Chains. Mol. Endocrinol. 14: 700-717 [Abstract] [Full Text]  
  • Hastings, M. L., Ingle, H. A., Lazar, M. A., Munroe, S. H. (2000). Post-transcriptional Regulation of Thyroid Hormone Receptor Expression by cis-Acting Sequences and a Naturally Occurring Antisense RNA. J. Biol. Chem. 275: 11507-11513 [Abstract] [Full Text]  
  • Laffitte, B. A., Kast, H. R., Nguyen, C. M., Zavacki, A. M., Moore, D. D., Edwards, P. A. (2000). Identification of the DNA Binding Specificity and Potential Target Genes for the Farnesoid X-activated Receptor. J. Biol. Chem. 275: 10638-10647 [Abstract] [Full Text]  
  • Busch, K., Martin, B., Baniahmad, A., Martial, J. A., Renkawitz, R., Muller, M. (2000). Silencing Subdomains of v-ErbA Interact Cooperatively with Corepressors: Involvement of Helices 5/6. Mol. Endocrinol. 14: 201-211 [Abstract] [Full Text]  
  • Chomez, P, Neveu, I, Mansen, A, Kiesler, E, Larsson, L, Vennstrom, B, Arenas, E (2000). Increased cell death and delayed development in the cerebellum of mice lacking the rev-erbA(alpha) orphan receptor. Development 127: 1489-1498 [Abstract]  
  • Giguère, V. (1999). Orphan Nuclear Receptors: From Gene to Function. Endocr. Rev. 20: 689-725 [Abstract] [Full Text]  
  • Atkins, G. B., Hu, X., Guenther, M. G., Rachez, C., Freedman, L. P., Lazar, M. A. (1999). Coactivators for the Orphan Nuclear Receptor ROR{alpha}. Mol. Endocrinol. 13: 1550-1557 [Abstract] [Full Text]  
  • Kassam, A., Capone, J. P., Rachubinski, R. A. (1999). Orphan Nuclear Hormone Receptor RevErbalpha Modulates Expression from the Promoter of the Hydratase-dehydrogenase Gene by Inhibiting Peroxisome Proliferator-activated Receptor alpha -Dependent Transactivation. J. Biol. Chem. 274: 22895-22900 [Abstract] [Full Text]  
  • Feltkamp, D., Wiebel, F. F., Alberti, S., Gustafsson, J.-A. (1999). Identification of a Novel DNA Binding Site for Nuclear Orphan Receptor OR1. J. Biol. Chem. 274: 10421-10429 [Abstract] [Full Text]  
  • Gervois, P., Chopin-Delannoy, S., Fadel, A., Dubois, G., Kosykh, V., Fruchart, J.-C., Najïb, J., Laudet, V., Staels, B. (1999). Fibrates Increase Human REV-ERB{alpha} Expression in Liver via a Novel Peroxisome Proliferator-Activated Receptor Response Element. Mol. Endocrinol. 13: 400-409 [Abstract] [Full Text]  
  • Moraitis, A. N., Giguère, V. (1999). Transition from Monomeric to Homodimeric DNA Binding by Nuclear Receptors: Identification of RevErbA{alpha} Determinants Required for ROR{alpha} Homodimer Complex Formation. Mol. Endocrinol. 13: 431-439 [Abstract] [Full Text]  
  • Reginato, M. J., Bailey, S. T., Krakow, S. L., Minami, C., Ishii, S., Tanaka, H., Lazar, M. A. (1998). A Potent Antidiabetic Thiazolidinedione with Unique Peroxisome Proliferator-activated Receptor gamma -activating Properties. J. Biol. Chem. 273: 32679-32684 [Abstract] [Full Text]  
  • Hsu, M.-H., Palmer, C. N. A., Song, W., Griffin, K. J., Johnson, E. F. (1998). A Carboxyl-terminal Extension of the Zinc Finger Domain Contributes to the Specificity and Polarity of Peroxisome Proliferator-activated Receptor DNA Binding. J. Biol. Chem. 273: 27988-27997 [Abstract] [Full Text]  
  • Vu-Dac, N., Chopin-Delannoy, S., Gervois, P., Bonnelye, E., Martin, G., Fruchart, J.-C., Laudet, V., Staels, B. (1998). The Nuclear Receptors Peroxisome Proliferator-activated Receptor alpha  and Rev-erbalpha Mediate the Species-specific Regulation of Apolipoprotein A-I Expression by Fibrates. J. Biol. Chem. 273: 25713-25720 [Abstract] [Full Text]  
  • Zhang, J., Guenther, M. G., Carthew, R. W., Lazar, M. A. (1998). Proteasomal regulation of nuclear receptor corepressor-mediated repression. Genes Dev. 12: 1775-1780 [Abstract] [Full Text]  
  • Burke, L. J., Downes, M., Laudet, V., Muscat, G. E. O. (1998). Identification and Characterization of a Novel Corepressor Interaction Region in RVR and Rev-erbA{alpha}. Mol. Endocrinol. 12: 248-262 [Abstract] [Full Text]  
  • Zamir, I., Dawson, J., Lavinsky, R. M., Glass, C. K., Rosenfeld, M. G., Lazar, M. A. (1997). Cloning and characterization of a corepressor and potential component of the nuclear hormone receptor repression complex. Proc. Natl. Acad. Sci. USA 94: 14400-14405 [Abstract] [Full Text]  
  • Harding, H. P., Atkins, G. B., Jaffe, A. B., Seo, W. J., Lazar, M. A. (1997). Transcriptional Activation and Repression by ROR{alpha}, an Orphan Nuclear Receptor Required for Cerebellar Development. Mol. Endocrinol. 11: 1737-1746 [Abstract] [Full Text]  
  • Zamir, I, Zhang, J, Lazar, M A (1997). Stoichiometric and steric principles governing repression by nuclear hormone receptors.. Genes Dev. 11: 835-846 [Abstract]  
  • Johnston, S. D., Liu, X., Zuo, F., Eisenbraun, T. L., Wiley, S. R., Kraus, R. J., Mertz, J. E. (1997). Estrogen-Related Receptor {alpha}1 Functionally Binds as a Monomer to Extended Half-Site Sequences Including Ones Contained within Estrogen-Response Elements. Mol. Endocrinol. 11: 342-352 [Abstract] [Full Text]  
  • Lam, G., Jiang, C, Thummel, C. (1997). Coordination of larval and prepupal gene expression by the DHR3 orphan receptor during Drosophila metamorphosis. Development 124: 1757-1769 [Abstract]  
  • Reginato, M. J., Zhang, J., Lazar, M. A. (1996). DNA-independent and DNA-dependent Mechanisms Regulate the Differential Heterodimerization of the Isoforms of the Thyroid Hormone Receptor with Retinoid X Receptor. J. Biol. Chem. 271: 28199-28205 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»