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 McPhillips, M. G.
Right arrow Articles by McBride, A. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McPhillips, M. G.
Right arrow Articles by McBride, A. A.

 Previous Article  |  Next Article 

Journal of Virology, July 2005, p. 8920-8932, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.8920-8932.2005

Interaction of Bovine Papillomavirus E2 Protein with Brd4 Stabilizes Its Association with Chromatin

Maria G. McPhillips,1 Keiko Ozato,2 and Alison A. McBride1*

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,1 Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland2

Received 21 December 2004/ Accepted 29 March 2005

The bovine papillomavirus E2 protein maintains and segregates the viral extrachromosomal genomes by tethering them to cellular mitotic chromosomes. E2 interacts with a cellular bromodomain protein, Brd4, to mediate the segregation of viral genomes into daughter cells. Brd4 binds acetylated histones and has been observed to diffusely coat mitotic chromosomes in several cell types. In this study, we show that in mitotic C127 cells, Brd4 diffusely coated the condensed chromosomes. However, in the presence of the E2 protein, E2 and Brd4 colocalized in punctate dots that were randomly distributed over the chromosomes. A similar pattern of E2 and Brd4 colocalization on mitotic chromosomes was observed in CV-1 cells, whereas only a faint chromosomal coating of Brd4 was detected in the absence of the E2 protein. Therefore, the viral E2 protein relocalizes and/or stabilizes the association of Brd4 with chromosomes in mitotic cells. The colocalization of E2 and Brd4 was also observed in interphase cells, indicating that this protein-protein interaction persists throughout the cell cycle. The interaction of E2 with Brd4 greatly stabilized the association of Brd4 with interphase chromatin. In both mitotic and interphase cells, this stabilization required a transcriptionally competent transactivation domain, but not the DNA binding function of the E2 protein. Thus, the E2 protein modulates the chromatin association of Brd4 during both interphase and mitosis. This study demonstrates that the segregation of papillomavirus genomes is not simply due to the passive hitchhiking of the E2/genome complex with a convenient cellular chromosomal protein.

* Corresponding author. Mailing address: Laboratory of Viral Diseases, NIAID, NIH, Building 4, Room 137, 4 Center Dr., MSC 0455, Bethesda, MD 20892-0455. Phone: (301) 496-1370. Fax: (301) 480-1497. E-mail: amcbride{at}nih.gov.

Journal of Virology, July 2005, p. 8920-8932, Vol. 79, No. 14
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.14.8920-8932.2005




This article has been cited by other articles:

  • Feeney, K. M, Parish, J. L (2009). Targeting mitotic chromosomes: a conserved mechanism to ensure viral genome persistence. Proc R Soc B 276: 1535-1544 [Abstract] [Full Text]  
  • Kelley-Clarke, B., De Leon-Vazquez, E., Slain, K., Barbera, A. J., Kaye, K. M. (2009). Role of Kaposi's Sarcoma-Associated Herpesvirus C-Terminal LANA Chromosome Binding in Episome Persistence. J. Virol. 83: 4326-4337 [Abstract] [Full Text]  
  • Ottinger, M., Pliquet, D., Christalla, T., Frank, R., Stewart, J. P., Schulz, T. F. (2009). The Interaction of the Gammaherpesvirus 68 orf73 Protein with Cellular BET Proteins Affects the Activation of Cell Cycle Promoters. J. Virol. 83: 4423-4434 [Abstract] [Full Text]  
  • Jang, M. K., Kwon, D., McBride, A. A. (2009). Papillomavirus E2 Proteins and the Host Brd4 Protein Associate with Transcriptionally Active Cellular Chromatin. J. Virol. 83: 2592-2600 [Abstract] [Full Text]  
  • Poddar, A., Reed, S. C., McPhillips, M. G., Spindler, J. E., McBride, A. A. (2009). The Human Papillomavirus Type 8 E2 Tethering Protein Targets the Ribosomal DNA Loci of Host Mitotic Chromosomes. J. Virol. 83: 640-650 [Abstract] [Full Text]  
  • Lin, A., Wang, S., Nguyen, T., Shire, K., Frappier, L. (2008). The EBNA1 Protein of Epstein-Barr Virus Functionally Interacts with Brd4. J. Virol. 82: 12009-12019 [Abstract] [Full Text]  
  • Cardenas-Mora, J., Spindler, J. E., Jang, M. K., McBride, A. A. (2008). Dimerization of the Papillomavirus E2 Protein Is Required for Efficient Mitotic Chromosome Association and Brd4 Binding. J. Virol. 82: 7298-7305 [Abstract] [Full Text]  
  • Yang, Z., He, N., Zhou, Q. (2008). Brd4 Recruits P-TEFb to Chromosomes at Late Mitosis To Promote G1 Gene Expression and Cell Cycle Progression. Mol. Cell. Biol. 28: 967-976 [Abstract] [Full Text]  
  • Schweiger, M.-R., Ottinger, M., You, J., Howley, P. M. (2007). Brd4-Independent Transcriptional Repression Function of the Papillomavirus E2 Proteins. J. Virol. 81: 9612-9622 [Abstract] [Full Text]  
  • Bisgrove, D. A., Mahmoudi, T., Henklein, P., Verdin, E. (2007). Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription. Proc. Natl. Acad. Sci. USA 104: 13690-13695 [Abstract] [Full Text]  
  • Nagashima, T., Maruyama, T., Furuya, M., Kajitani, T., Uchida, H., Masuda, H., Ono, M., Arase, T., Ozato, K., Yoshimura, Y. (2007). Histone acetylation and subcellular localization of chromosomal protein BRD4 during mouse oocyte meiosis and mitosis. Mol Hum Reprod 13: 141-148* [Abstract] [Full Text]  
  • Yu, T., Peng, Y.-C., Androphy, E. J. (2007). Mitotic Kinesin-Like Protein 2 Binds and Colocalizes with Papillomavirus E2 during Mitosis. J. Virol. 81: 1736-1745 [Abstract] [Full Text]  
  • McPhillips, M. G., Oliveira, J. G., Spindler, J. E., Mitra, R., McBride, A. A. (2006). Brd4 Is Required for E2-Mediated Transcriptional Activation but Not Genome Partitioning of All Papillomaviruses. J. Virol. 80: 9530-9543 [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]  
  • Schweiger, M.-R., You, J., Howley, P. M. (2006). Bromodomain Protein 4 Mediates the Papillomavirus E2 Transcriptional Activation Function. J. Virol. 80: 4276-4285 [Abstract] [Full Text]  
  • Ilves, I., Maemets, K., Silla, T., Janikson, K., Ustav, M. (2006). Brd4 is involved in multiple processes of the bovine papillomavirus type 1 life cycle.. J. Virol. 80: 3660-3665 [Abstract] [Full Text]  
  • Oliveira, J. G., Colf, L. A., McBride, A. A. (2006). Variations in the association of papillomavirus E2 proteins with mitotic chromosomes. Proc. Natl. Acad. Sci. USA 103: 1047-1052 [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»