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Journal of Virology, December 2008, p. 12009-12019, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01680-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The EBNA1 Protein of Epstein-Barr Virus Functionally Interacts with Brd4{triangledown}

Ammy Lin, Shan Wang, Tin Nguyen, Kathy Shire, and Lori Frappier*

Department of Molecular Genetics, University of Toronto, 1 Kings College Circle, Toronto, Canada M5S 1A8

Received 6 August 2008/ Accepted 6 October 2008

The EBNA1 protein of Epstein-Barr virus (EBV) is essential for EBV latent infection in ensuring the replication and stable segregation of the EBV genomes and in activating the transcription of other EBV latency genes. We have tested the ability of four host proteins (Brd2, Brd4, DEK, and MeCP2) implicated in the segregation of papillomavirus and Kaposi's sarcoma-associated herpesvirus to support EBNA1-mediated segregation of EBV-based plasmids in Saccharomyces cerevisiae. We found that Brd4 enabled EBNA1-mediated segregation while Brd2 and MeCP2 had a general stimulatory effect on plasmid maintenance. EBNA1 interacted with Brd4 in both yeast and human cells through N-terminal sequences previously shown to mediate transcriptional activation but not segregation. In keeping with this interaction site, silencing of Brd4 in human cells decreased transcriptional activation by EBNA1 but not the mitotic chromosome attachment of EBNA1 that is required for segregation. In addition, Brd4 was found to be preferentially localized to the FR enhancer element regulated by EBNA1, over other EBV sequences, in latently EBV-infected cells. The results indicate that EBNA1 can functionally interact with Brd4 in native and heterologous systems and that this interaction facilitates transcriptional activation by EBNA1 from the FR element.


* Corresponding author. Mailing address: Department of Molecular Genetics, University of Toronto, 1 Kings College Circle, Toronto, Canada M5S 1A8. Phone: (416) 946-3501. Fax: (416) 978-6885. E-mail: lori.frappier{at}utoronto.ca

{triangledown} Published ahead of print on 15 October 2008.


Journal of Virology, December 2008, p. 12009-12019, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01680-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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