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 Stünkel, W.
Right arrow Articles by Bernard, H.-U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stünkel, W.
Right arrow Articles by Bernard, H.-U.

 Previous Article  |  Next Article 

Journal of Virology, March 1999, p. 1918-1930, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Chromatin Structure of the Long Control Region of Human Papillomavirus Type 16 Represses Viral Oncoprotein Expression

Walter Stünkel and Hans-Ulrich Bernard*

Institute of Molecular and Cell Biology, National University of Singapore, Republic of Singapore

Received 2 September 1998/Accepted 20 November 1998

The long control region (LCR) of human papillomavirus type 16 (HPV-16) has a size of 850 bp (about 12% of the viral genome) and regulates transcription and replication of the viral DNA. The 5' segment of the LCR contains transcription termination signals and a nuclear matrix attachment region, the central segment contains an epithelial cell-specific enhancer, and the 3' segment contains the replication origin and the E6 promoter. Here we report observations on the chromatin organization of this part of the HPV-16 genome. Treatment of the nuclei of CaSki cells, a cell line with 500 intrachromosomal copies of HPV-16, with methidiumpropyl-EDTA-Fe(II) reveals nucleosomes in specific positions on the LCR and the E6 and E7 genes. One of these nucleosomes, which we termed Ne, overlaps with the center of the viral enhancer, while a second nucleosome, Np16, overlaps with the replication origin and the E6 promoter. The two nucleosomes become positioned on exactly the same segments after in vitro assembly of chromatin on the cloned HPV-16 LCR. Primer extension mapping of DNase I-cleaved chromatin revealed Np16 to be positioned centrally over E6 promoter elements, extending into the replication origin. Ne covers the center of the enhancer but leaves an AP-1 site, one of the strongest cis-responsive elements of the enhancer, unprotected. Np16, or a combination of Np16 and Ne, represses the activity of the E6 promoter during in vitro transcription of HPV-16 chromatin. Repression is relieved by addition of Sp1 and AP-1 transcription factors. Sp1 alters the structure of Np16 in vitro, while no changes can be observed during the binding of AP-1. HPV-18, which has a similar arrangement of cis-responsive elements despite its evolutionary divergence from HPV-16, shows specific assembly in vitro of a nucleosome, Np18, over the E1 binding site and E6 promoter elements but positioned about 90 bp 5' of the position of Np16 on the homologous HPV-16 sequences. The chromatin organization of the HPV-16 and HPV-18 genomes suggests important regulatory roles of nucleosomes during the viral life cycle.

* Corresponding author. Mailing address: Institute of Molecular and Cell Biology, National University of Singapore, 30 Medical Dr., Singapore 117609. Phone: 65-874-3755. Fax: 65-779-1117. E-mail: mcbhub{at}mcbsgs1.imcb.nus.edu.sg.

Journal of Virology, March 1999, p. 1918-1930, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Lazarczyk, M., Cassonnet, P., Pons, C., Jacob, Y., Favre, M. (2009). The EVER Proteins as a Natural Barrier against Papillomaviruses: a New Insight into the Pathogenesis of Human Papillomavirus Infections. Microbiol. Mol. Biol. Rev. 73: 348-370 [Abstract] [Full Text]  
  • Jia, R., Liu, X., Tao, M., Kruhlak, M., Guo, M., Meyers, C., Baker, C. C., Zheng, Z.-M. (2009). Control of the Papillomavirus Early-to-Late Switch by Differentially Expressed SRp20. J. Virol. 83: 167-180 [Abstract] [Full Text]  
  • Vartanian, J.-P., Guetard, D., Henry, M., Wain-Hobson, S. (2008). Evidence for Editing of Human Papillomavirus DNA by APOBEC3 in Benign and Precancerous Lesions. Science 320: 230-233 [Abstract] [Full Text]  
  • Wu, S.-Y., Lee, A-Y., Hou, S. Y., Kemper, J. K., Erdjument-Bromage, H., Tempst, P., Chiang, C.-M. (2006). Brd4 links chromatin targeting to HPV transcriptional silencing. Genes Dev. 20: 2383-2396 [Abstract] [Full Text]  
  • Kalantari, M., Calleja-Macias, I. E., Tewari, D., Hagmar, B., Lie, K., Barrera-Saldana, H. A., Wiley, D. J., Bernard, H.-U. (2004). Conserved Methylation Patterns of Human Papillomavirus Type 16 DNA in Asymptomatic Infection and Cervical Neoplasia. J. Virol. 78: 12762-12772 [Abstract] [Full Text]  
  • Rosenstierne, M. W., Vinther, J., Hansen, C. N., Prydsoe, M., Norrild, B. (2003). Identification and characterization of a cluster of transcription start sites located in the E6 ORF of human papillomavirus type 16. J. Gen. Virol. 84: 2909-2920 [Abstract] [Full Text]  
  • Badal, V., Chuang, L. S. H., Tan, E. H.-H., Badal, S., Villa, L. L., Wheeler, C. M., Li, B. F. L., Bernard, H.-U. (2003). CpG Methylation of Human Papillomavirus Type 16 DNA in Cervical Cancer Cell Lines and in Clinical Specimens: Genomic Hypomethylation Correlates with Carcinogenic Progression. J. Virol. 77: 6227-6234 [Abstract] [Full Text]  
  • Pena, L. d. M., Laimins, L. A. (2001). Differentiation-Dependent Chromatin Rearrangement Coincides with Activation of Human Papillomavirus Type 31 Late Gene Expression. J. Virol. 75: 10005-10013 [Abstract] [Full Text]  
  • Vance, K. W., Campo, M. S., Morgan, I. M. (2001). A Novel Silencer Element in the Bovine Papillomavirus Type 4 Promoter Represses the Transcriptional Response to Papillomavirus E2 Protein. J. Virol. 75: 2829-2838 [Abstract] [Full Text]  
  • Tornesello, M. L., Buonaguro, F. M., Buonaguro, L., Salatiello, I., Beth-Giraldo, E., Giraldo, G. (2000). Identification and functional analysis of sequence rearrangements in the long control region of human papillomavirus type 16 Af-1 variants isolated from Ugandan penile carcinomas. J. Gen. Virol. 81: 2969-2982 [Abstract] [Full Text]  
  • Nishimura, A., Ono, T., Ishimoto, A., Dowhanick, J. J., Frizzell, M. A., Howley, P. M., Sakai, H. (2000). Mechanisms of Human Papillomavirus E2-Mediated Repression of Viral Oncogene Expression and Cervical Cancer Cell Growth Inhibition. J. Virol. 74: 3752-3760 [Abstract] [Full Text]  
  • Stünkel, W., Huang, Z., Tan, S.-H., O'Connor, M. J., Bernard, H.-U. (2000). Nuclear Matrix Attachment Regions of Human Papillomavirus Type 16 Repress or Activate the E6 Promoter, Depending on the Physical State of the Viral DNA. J. Virol. 74: 2489-2501 [Abstract] [Full Text]  
  • O'Connor, M. J., Stünkel, W., Koh, C.-H., Zimmermann, H., Bernard, H.-U. (2000). The Differentiation-Specific Factor CDP/Cut Represses Transcription and Replication of Human Papillomaviruses through a Conserved Silencing Element. J. Virol. 74: 401-410 [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»