This Article
Right arrow Full Text
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 Algarté, M.
Right arrow Articles by Hiscott, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Algarté, M.
Right arrow Articles by Hiscott, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 1999, p. 6140-6153, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Identification by In Vivo Genomic Footprinting of a Transcriptional Switch Containing NF-kappa B and Sp1 That Regulates the Ikappa Balpha Promoter

Michèle Algarté, Hakju Kwon, Pierre Génin, and John Hiscott*

Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, and Departments of Microbiology & Immunology, Medicine, and Oncology, McGill University, Montreal, Canada H3T 1E2

Received 8 April 1999/Returned for modification 10 May 1999/Accepted 9 June 1999

In unstimulated cells, NF-kappa B transcription factors are retained in the cytoplasm by inhibitory Ikappa B proteins. Upon stimulation by multiple inducers including cytokines or viruses, Ikappa Balpha is rapidly phosphorylated and degraded, resulting in the release of NF-kappa B and the subsequent increase in NF-kappa B-regulated gene expression. Ikappa Balpha gene expression is also regulated by an NF-kappa B autoregulatory mechanism, via NF-kappa B binding sites in the Ikappa Balpha promoter. In previous studies, tetracycline-inducible expression of transdominant repressors of Ikappa Balpha (TD-Ikappa Balpha ) progressively decreased endogenous Ikappa Balpha protein levels. In the present study, we demonstrate that expression of TD-Ikappa Balpha blocked phorbol myristate acetate-phytohemagglutinin or tumor necrosis factor alpha-induced Ikappa Balpha gene transcription and abolished NF-kappa B DNA binding activity, due to the continued cytoplasmic sequestration of RelA(p65) by TD-Ikappa Balpha . In vivo genomic footprinting revealed stimulus-responsive protein-DNA binding not only to the -63 to -53 kappa B1 site but also to the adjacent -44 to -36 Sp1 site of the Ikappa Balpha promoter. In vivo protection of both sites was inhibited by tetracycline-inducible TD-Ikappa Balpha expression. Prolonged NF-kappa B binding and a temporal switch in the composition of NF-kappa B complexes bound to the -63 to -53 kappa B1 site of the Ikappa Balpha promoter were also observed; with time after induction, decreased levels of transcriptionally active p50-p65 and increased p50-c-Rel heterodimers were detected at the kappa B1 site. Mutation of either the kappa B1 site or the Sp1 site abolished transcription factor binding to the respective sites and the inducibility of the Ikappa Balpha promoter in transient transfection studies. These observations provide the first in vivo characterization of a promoter proximal transcriptional switch involving NF-kappa B and Sp1 that is essential for autoregulation of the Ikappa Balpha promoter.

* Corresponding author. Mailing address: Lady Davis Institute for Medical Research, 3755 Cote Ste. Catherine, Montreal, Quebec, Canada H3T1E2. Phone: (514) 340-8222, ext. 5265. Fax: (514) 340-7576. E-mail: mijh{at}musica.mcgill.ca.

Molecular and Cellular Biology, September 1999, p. 6140-6153, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Lee, J. W., Wang, P., Kattah, M. G., Youssef, S., Steinman, L., DeFea, K., Straus, D. S. (2008). Differential Regulation of Chemokines by IL-17 in Colonic Epithelial Cells. J. Immunol. 181: 6536-6545 [Abstract] [Full Text]  
  • Sgarbanti, M., Remoli, A. L., Marsili, G., Ridolfi, B., Borsetti, A., Perrotti, E., Orsatti, R., Ilari, R., Sernicola, L., Stellacci, E., Ensoli, B., Battistini, A. (2008). IRF-1 Is Required for Full NF-{kappa}B Transcriptional Activity at the Human Immunodeficiency Virus Type 1 Long Terminal Repeat Enhancer. J. Virol. 82: 3632-3641 [Abstract] [Full Text]  
  • Caposio, P., Gugliesi, F., Zannetti, C., Sponza, S., Mondini, M., Medico, E., Hiscott, J., Young, H. A., Gribaudo, G., Gariglio, M., Landolfo, S. (2007). A Novel Role of the Interferon-inducible Protein IFI16 as Inducer of Proinflammatory Molecules in Endothelial Cells. J. Biol. Chem. 282: 33515-33529 [Abstract] [Full Text]  
  • Horion, J., Gloire, G., El Mjiyad, N., Quivy, V., Vermeulen, L., Vanden Berghe, W., Haegeman, G., Van Lint, C., Piette, J., Habraken, Y. (2007). Histone Deacetylase Inhibitor Trichostatin A Sustains Sodium Pervanadate-induced NF-{kappa}B Activation by Delaying I{kappa}B{alpha} mRNA Resynthesis: COMPARISON WITH TUMOR NECROSIS FACTOR {alpha}. J. Biol. Chem. 282: 15383-15393 [Abstract] [Full Text]  
  • Nogalski, M. T., Podduturi, J. P., DeMeritt, I. B., Milford, L. E., Yurochko, A. D. (2007). The Human Cytomegalovirus Virion Possesses an Activated Casein Kinase II That Allows for the Rapid Phosphorylation of the Inhibitor of NF-{kappa}B, I{kappa}B{alpha}. J. Virol. 81: 5305-5314 [Abstract] [Full Text]  
  • Luecke, H. F., Yamamoto, K. R. (2005). The glucocorticoid receptor blocks P-TEFb recruitment by NF{kappa}B to effect promoter-specific transcriptional repression. Genes Dev. 19: 1116-1127 [Abstract] [Full Text]  
  • De Bosscher, K., Vanden Berghe, W., Haegeman, G. (2003). The Interplay between the Glucocorticoid Receptor and Nuclear Factor-{kappa}B or Activator Protein-1: Molecular Mechanisms for Gene Repression. Endocr. Rev. 24: 488-522 [Abstract] [Full Text]  
  • Oakley, F., Mann, J., Ruddell, R. G., Pickford, J., Weinmaster, G., Mann, D. A. (2003). Basal Expression of I{kappa}B{alpha} Is Controlled by the Mammalian Transcriptional Repressor RBP-J (CBF1) and Its Activator Notch1. J. Biol. Chem. 278: 24359-24370 [Abstract] [Full Text]  
  • Sharma, S., Grandvaux, N., Mamane, Y., Genin, P., Azimi, N., Waldmann, T., Hiscott, J. (2002). Regulation of IFN Regulatory Factor 4 Expression in Human T Cell Leukemia Virus-I-Transformed T Cells. J. Immunol. 169: 3120-3130 [Abstract] [Full Text]  
  • Kuang, P.-P., Berk, J. L., Rishikof, D. C., Foster, J. A., Humphries, D. E., Ricupero, D. A., Goldstein, R. H. (2002). NF-kappa B induced by IL-1beta inhibits elastin transcription and myofibroblast phenotype. Am. J. Physiol. Cell Physiol. 283: C58-C65 [Abstract] [Full Text]  
  • Delerive, P., De Bosscher, K., Vanden Berghe, W., Fruchart, J.-C., Haegeman, G., Staels, B. (2002). DNA Binding-Independent Induction of I{kappa}B{alpha} Gene Transcription by PPAR{alpha}. Mol. Endocrinol. 16: 1029-1039 [Abstract] [Full Text]  
  • Bachmann, A., Hanke, B., Zawatzky, R., Soto, U., van Riggelen, J., zur Hausen, H., Rosl, F. (2002). Disturbance of Tumor Necrosis Factor Alpha-Mediated Beta Interferon Signaling in Cervical Carcinoma Cells. J. Virol. 76: 280-291 [Abstract] [Full Text]  
  • Deroo, B. J., Archer, T. K. (2001). Glucocorticoid Receptor Activation of the Ikappa Balpha Promoter within Chromatin. Mol. Biol. Cell 12: 3365-3374 [Abstract] [Full Text]  
  • Gelfanov, V. M., Burgess, G. S., Litz-Jackson, S., King, A. J., Marshall, M. S., Nakshatri, H., Boswell, H. S. (2001). Transformation of interleukin-3-dependent cells without participation of Stat5/bcl-xL: cooperation of akt with raf/erk leads to p65 nuclear factor {kappa}B-mediated antiapoptosis involving c-IAP2. Blood 98: 2508-2517 [Abstract] [Full Text]  
  • Baetu, T. M., Kwon, H., Sharma, S., Grandvaux, N., Hiscott, J. (2001). Disruption of NF-{kappa}B Signaling Reveals a Novel Role for NF-{kappa}B in the Regulation of TNF-Related Apoptosis-Inducing Ligand Expression. J. Immunol. 167: 3164-3173 [Abstract] [Full Text]  
  • Genin, P., Algarte, M., Roof, P., Lin, R., Hiscott, J. (2000). Regulation of RANTES Chemokine Gene Expression Requires Cooperativity Between NF-{kappa}B and IFN-Regulatory Factor Transcription Factors. J. Immunol. 164: 5352-5361 [Abstract] [Full Text]  
  • Heylbroeck, C., Balachandran, S., Servant, M. J., DeLuca, C., Barber, G. N., Lin, R., Hiscott, J. (2000). The IRF-3 Transcription Factor Mediates Sendai Virus-Induced Apoptosis. J. Virol. 74: 3781-3792 [Abstract] [Full Text]  
  • Tanaka, N., Yonekura, H., Yamagishi, S.-i., Fujimori, H., Yamamoto, Y., Yamamoto, H. (2000). The Receptor for Advanced Glycation End Products Is Induced by the Glycation Products Themselves and Tumor Necrosis Factor-alpha through Nuclear Factor-kappa B, and by 17beta -Estradiol through Sp-1 in Human Vascular Endothelial Cells. J. Biol. Chem. 275: 25781-25790 [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»