TY - JOUR
T1 - EBNA1 regulates cellular gene expression by binding cellular promoters
AU - Canaan, Allon
AU - Haviv, Izhak
AU - Urban, Alexander E.
AU - Schulz, Vincent P.
AU - Hartman, Steve
AU - Zhang, Zhengdong
AU - Palejev, Dean
AU - Deisseroth, Albert B.
AU - Lacy, Jill
AU - Snyder, Michael
AU - Gerstein, Mark
AU - Weissman, Sherman M.
PY - 2009/12/29
Y1 - 2009/12/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=76049087454&partnerID=8YFLogxK
U2 - 10.1073/pnas.0911676106
DO - 10.1073/pnas.0911676106
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C2 - 20080792
AN - SCOPUS:76049087454
SN - 0027-8424
VL - 106
SP - 22421
EP - 22426
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 52
ER -
