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 Ragoczy, T.
Right arrow Articles by Miller, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ragoczy, T.
Right arrow Articles by Miller, G.

 Previous Article  |  Next Article 

Journal of Virology, June 2001, p. 5240-5251, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5240-5251.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Autostimulation of the Epstein-Barr Virus BRLF1 Promoter Is Mediated through Consensus Sp1 and Sp3 Binding Sites

Tobias Ragoczy1 and George Miller2,*

Departments of Molecular Biophysics and Biochemistry1 and Pediatrics and Epidemiology and Public Health,2 Yale School of Medicine, New Haven, Connecticut 06520

Received 1 December 2000/Accepted 9 March 2001

As an essential step in the lytic cascade, the Rta homologues of gammaherpesviruses all activate their own expression. Consistent with this biologic function, the Epstein-Barr virus (EBV) Rta protein powerfully stimulates the promoter of its own gene, Rp, in EBV-positive B cells in transient-transfection reporter-based assays. We analyzed the activity of RpCAT in response to Rta by deletional and site-directed mutagenesis. Two cognate Sp1 binding sites located at -279 and -45 relative to the transcriptional start site proved crucial for Rta-mediated activation. Previously described binding sites for the cellular transcription factor Zif268 and the viral transactivator ZEBRA were found to be dispensable for activation of RpCAT by Rta. Gel shift analysis, using extracts of B cells in latency or induced into the lytic cycle, identified Sp1 and Sp3 as the predominant cellular proteins bound to Rp near -45. During the lytic cycle, ZEBRA bound Rp near the Sp1/Sp3 site. The binding of Sp1 and Sp3 to Rp correlated with the reporter activities in the mutagenesis study, establishing a direct link between transcriptional activation of Rp by Rta and DNA binding by Sp1 and/or Sp3. The relative abundance or functional state of the cellular Sp1 and Sp3 transcription factors may be altered in response to stimuli that induce the BRLF1 promoter and thereby contribute to the activation of the viral lytic cycle.

* Corresponding author. Mailing address: Department of Pediatrics, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520. Phone: (203) 785-4758. Fax: (203) 785-6961. E-mail: George.Miller{at}yale.edu.

Journal of Virology, June 2001, p. 5240-5251, Vol. 75, No. 11
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.11.5240-5251.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Verma, D., Ling, C., Johannsen, E., Nagaraja, T., Swaminathan, S. (2009). Negative Autoregulation of Epstein-Barr Virus (EBV) Replicative Gene Expression by EBV SM Protein. J. Virol. 83: 8041-8050 [Abstract] [Full Text]  
  • Chang, P.-J., Shedd, D., Miller, G. (2008). A Mobile Functional Region of Kaposi's Sarcoma-Associated Herpesvirus ORF50 Protein Independently Regulates DNA Binding and Protein Abundance. J. Virol. 82: 9700-9716 [Abstract] [Full Text]  
  • Calderwood, M. A., Holthaus, A. M., Johannsen, E. (2008). The Epstein-Barr Virus LF2 Protein Inhibits Viral Replication. J. Virol. 82: 8509-8519 [Abstract] [Full Text]  
  • Countryman, J. K., Gradoville, L., Miller, G. (2008). Histone Hyperacetylation Occurs on Promoters of Lytic Cycle Regulatory Genes in Epstein-Barr Virus-Infected Cell Lines Which Are Refractory to Disruption of Latency by Histone Deacetylase Inhibitors. J. Virol. 82: 4706-4719 [Abstract] [Full Text]  
  • Chia, M. C., Leung, A., Krushel, T., Alajez, N. M., Lo, K. W., Busson, P., Klamut, H. J., Bastianutto, C., Liu, F.-F. (2008). Nuclear Factor-Y and Epstein Barr Virus in Nasopharyngeal Cancer. Clin. Cancer Res. 14: 984-994 [Abstract] [Full Text]  
  • Lee, S., Cho, H.-J., Park, J.-J., Kim, Y.-S., Hwang, S., Sun, R., Song, M. J. (2007). The ORF49 Protein of Murine Gammaherpesvirus 68 Cooperates with RTA in Regulating Virus Replication. J. Virol. 81: 9870-9877 [Abstract] [Full Text]  
  • Ye, J., Gradoville, L., Daigle, D., Miller, G. (2007). De Novo Protein Synthesis Is Required for Lytic Cycle Reactivation of Epstein-Barr Virus, but Not Kaposi's Sarcoma-Associated Herpesvirus, in Response to Histone Deacetylase Inhibitors and Protein Kinase C Agonists. J. Virol. 81: 9279-9291 [Abstract] [Full Text]  
  • Ho, C.-H., Hsu, C.-F., Fong, P.-F., Tai, S.-K., Hsieh, S.-L., Chen, C.-J. (2007). Epstein-Barr Virus Transcription Activator Rta Upregulates Decoy Receptor 3 Expression by Binding to Its Promoter. J. Virol. 81: 4837-4847 [Abstract] [Full Text]  
  • Chua, H.-H., Lee, H.-H., Chang, S.-S., Lu, C.-C., Yeh, T.-H., Hsu, T.-Y., Cheng, T.-H., Cheng, J.-T., Chen, M.-R., Tsai, C.-H. (2007). Role of the TSG101 Gene in Epstein-Barr Virus Late Gene Transcription. J. Virol. 81: 2459-2471 [Abstract] [Full Text]  
  • Chang, L.-K., Chung, J.-Y., Hong, Y.-R., Ichimura, T., Nakao, M., Liu, S.-T. (2005). Activation of Sp1-mediated transcription by Rta of Epstein-Barr virus via an interaction with MCAF1. Nucleic Acids Res 33: 6528-6539 [Abstract] [Full Text]  
  • Chen, L.-W., Chang, P.-J., Delecluse, H.-J., Miller, G. (2005). Marked Variation in Response of Consensus Binding Elements for the Rta Protein of Epstein-Barr Virus. J. Virol. 79: 9635-9650 [Abstract] [Full Text]  
  • Walters, M. S., Hall, K. T., Whitehouse, A. (2005). The herpesvirus saimiri Rta gene autostimulates via binding to a non-consensus response element. J. Gen. Virol. 86: 581-587 [Abstract] [Full Text]  
  • Hsu, T.-Y., Chang, Y., Wang, P.-W., Liu, M.-Y., Chen, M.-R., Chen, J.-Y., Tsai, C.-H. (2005). Reactivation of Epstein-Barr virus can be triggered by an Rta protein mutated at the nuclear localization signal. J. Gen. Virol. 86: 317-322 [Abstract] [Full Text]  
  • Ye, J., Shedd, D., Miller, G. (2005). An Sp1 Response Element in the Kaposi's Sarcoma-Associated Herpesvirus Open Reading Frame 50 Promoter Mediates Lytic Cycle Induction by Butyrate. J. Virol. 79: 1397-1408 [Abstract] [Full Text]  
  • Chang, Y., Lee, H.-H., Chang, S.-S., Hsu, T.-Y., Wang, P.-W., Chang, Y.-S., Takada, K., Tsai, C.-H. (2004). Induction of Epstein-Barr Virus Latent Membrane Protein 1 by a Lytic Transactivator Rta. J. Virol. 78: 13028-13036 [Abstract] [Full Text]  
  • Chang, L.-K., Lee, Y.-H., Cheng, T.-S., Hong, Y.-R., Lu, P.-J., Wang, J. J., Wang, W.-H., Kuo, C.-W., Li, S. S.-L., Liu, S.-T. (2004). Post-translational Modification of Rta of Epstein-Barr Virus by SUMO-1. J. Biol. Chem. 279: 38803-38812 [Abstract] [Full Text]  
  • Kudoh, A., Daikoku, T., Sugaya, Y., Isomura, H., Fujita, M., Kiyono, T., Nishiyama, Y., Tsurumi, T. (2004). Inhibition of S-Phase Cyclin-Dependent Kinase Activity Blocks Expression of Epstein-Barr Virus Immediate-Early and Early Genes, Preventing Viral Lytic Replication. J. Virol. 78: 104-115 [Abstract] [Full Text]  
  • Lu, F., Zhou, J., Wiedmer, A., Madden, K., Yuan, Y., Lieberman, P. M. (2003). Chromatin Remodeling of the Kaposi's Sarcoma-Associated Herpesvirus ORF50 Promoter Correlates with Reactivation from Latency. J. Virol. 77: 11425-11435 [Abstract] [Full Text]  
  • Song, M. J., Deng, H., Sun, R. (2003). Comparative Study of Regulation of RTA-Responsive Genes in Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8. J. Virol. 77: 9451-9462 [Abstract] [Full Text]  
  • Roberts, B.T., Wickner, R. B. (2003). Heritable activity: a prion that propagates by covalent autoactivation. Genes Dev. 17: 2083-2087 [Abstract] [Full Text]  
  • Wang, X.-P., Gao, S.-J. (2003). Auto-activation of the transforming viral interferon regulatory factor encoded by Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8). J. Gen. Virol. 84: 329-336 [Abstract] [Full Text]  
  • Deng, H., Song, M. J., Chu, J. T., Sun, R. (2002). Transcriptional Regulation of the Interleukin-6 Gene of Human Herpesvirus 8 (Kaposi's Sarcoma-Associated Herpesvirus). J. Virol. 76: 8252-8264 [Abstract] [Full Text]  
  • Song, M. J., Li, X., Brown, H. J., Sun, R. (2002). Characterization of Interactions between RTA and the Promoter of Polyadenylated Nuclear RNA in Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8. J. Virol. 76: 5000-5013 [Abstract] [Full Text]  
  • Niller, H. H., Salamon, D., Uhlig, J., Ranf, S., Granz, M., Schwarzmann, F., Wolf, H., Minarovits, J. (2002). Nucleoprotein Structure of Immediate-Early Promoters Zp and Rp and of oriLyt of Latent Epstein-Barr Virus Genomes. J. Virol. 76: 4113-4118 [Abstract] [Full Text]  
  • Chang, P.-J., Shedd, D., Gradoville, L., Cho, M.-S., Chen, L.-W., Chang, J., Miller, G. (2002). Open Reading Frame 50 Protein of Kaposi's Sarcoma-Associated Herpesvirus Directly Activates the Viral PAN and K12 Genes by Binding to Related Response Elements. J. Virol. 76: 3168-3178 [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»