EBNA1 affinity column profiling identified interactions of EBNA1 with a family of nucleosome assembly proteins (Nap1, TAF-I alpha and TAF-I beta) known to have activating effects on transcription and DNA replication by affecting nucleosome-DNA interactions. We have found that these proteins contribute to the ability of EBNA1 to transactivate gene expression from the viral oriP enhancer element and to activate DNA replication from oriP. In addition, another nucleosome binding protein, Brd4, has been shown to bind the functional homologue of EBNA1 in papillomavirus (E2) and to be important for transcriptional activation by E2. We recently found that EBNA1 binds to Brd4 through EBNA1 sequences crucial for transcriptional activation and recruits it to the oriP enhancer element where it contributes to transcriptional activation. We are currently examining the mechanisms of all of these interactions and how they elicit their functional effects.

Publications:

Mansouri, S., Wang, S. and Frappier, L. 2013 A Role for the Nucleosome Assembly Proteins TAF-Iβ and NAP1 in Activation of BZLF1 Expression and Epstein-Barr Virus Reactivation. PLoS ONE 8(5):e63802. PMID:23691099

Wang, S. and Frappier, L. 2009 Nucleosome Assembly Proteins Bind to Epstein-Barr Nuclear Antigen 1 (EBNA1) and Affect its Functions in DNA Replication and Transcriptional Activation. J. Virol. 83, 11704-11714.

Lin, A., Wang, S., Nguyen, T., Shire, K. and Frappier, L. 2008 Functional Interactions Between the EBNA1 Protein of Epstein-Barr Virus and Brd4. J. Virol. 82, 12009-12012

Holowaty, M.N., Zeghouf, M., Wu, H., Tellam, J., Athanasopoulos, V., Greenblatt, J. and Frappier, L. 2003. Protein profiling with Epstein-Barr nuclear antigen 1 reveals an interaction with the herpesvirus associated ubiquitin specific protease, HAUSP/USP7. J.Biol. Chem., 29987-29994

Avolio-Hunter, T.M. and Frappier, L. 2003. EBNA1 efficiently assembles on chromatin containing the Epstein-Barr virus origin of replication, oriP. Virology 315, 398-408.

Avolio-Hunter, T., Lewis, P.N. and Frappier, L. 2001. Epstein-Barr nuclear antigen 1 binds and destabilizes nucleosomes at the viral origin of latent DNA replication. Nucl. Acids Res. 29, 3520-3528.