EBNA1 regulates cellular gene expression by binding cellular promoters

Allon Canaan, Izhak Haviv, Alexander E. Urban, Vincent P. Schulz, Steve Hartman, Zhengdong Zhang, Dean Palejev, Albert B. Deisseroth, Jill Lacy, Michael Snyder, Mark Gerstein, Sherman M. Weissman

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61 Scopus citations

Abstract

Epstein - Barr virus (EBV) is associated with several types of lymphomas and epithelial tumors including Burkitt's lymphoma (BL), HIV-associated lymphoma, posttransplant lymphoproliferative disorder, and nasopharyngeal carcinoma. EBV nuclear antigen 1 (EBNA1) is expressed in all EBV associated tumors and is required for latency and transformation. EBNA1 initiates latent viral replication in B cells, maintains the viral genome copy number, and regulates transcription of other EBV-encoded latent genes. These activities are mediated through the ability of EBNA1 to bind viral-DNA. To further elucidate the role of EBNA1 in the host cell, we have examined the effect of EBNA1 on cellular gene expression by microarray analysis using the B cell BJAB and the epithelial 293 cell lines transfected with EBNA1. Analysis of the data revealed distinct profiles of cellular gene changes in BJAB and 293 cell lines. Subsequently, chromatin immuneprecipitation revealed a direct binding ofEBNA1to cellular promoters. We have correlated EBNA1 bound promoters with changes in gene expression. Sequence analysis of the 100 promoters most enriched revealed a DNA motif that differs from the EBNA1 binding site in the EBV genome.

Original languageEnglish (US)
Pages (from-to)22421-22426
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number52
DOIs
StatePublished - Dec 19 2009
Externally publishedYes

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    Canaan, A., Haviv, I., Urban, A. E., Schulz, V. P., Hartman, S., Zhang, Z., Palejev, D., Deisseroth, A. B., Lacy, J., Snyder, M., Gerstein, M., & Weissman, S. M. (2009). EBNA1 regulates cellular gene expression by binding cellular promoters. Proceedings of the National Academy of Sciences of the United States of America, 106(52), 22421-22426. https://doi.org/10.1073/pnas.0911676106