EBNA1 regulates cellular gene expression by binding cellular promoters.
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 immune-precipitation revealed a direct binding of EBNA1 to 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.
Canaan
Allon
A
Department of Genetics, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, USA. allon.canaan@yale.edu
Haviv
Izhak
I
Urban
Alexander E
AE
Schulz
Vincent P
VP
Hartman
Steve
S
Zhang
Zhengdong
Z
Palejev
Dean
D
Deisseroth
Albert B
AB
Lacy
Jill
J
Snyder
Michael
M
Gerstein
Mark
M
Weissman
Sherman M
SM
D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics* / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D019309:Epstein-Barr Virus Nuclear Antigens; C417029:EBV-encoded nuclear antigen 1