Transcription profiling of Epstein-Barr virus nuclear antigen (EBNA)-1 expressing cells suggests targeting of chromatin remodeling complexes

• Published in: PloS one Vol. 5; no. 8; p. e12052
• Main Authors: Sompallae, Ramakrishna, Callegari, Simone, Kamranvar, Siamak Akbari, Masucci, Maria G
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10-08-2010; Public Library of Science (PLoS)
• Subjects: Analysis; Antigens; Apoptosis; B-cell lymphoma; Binding sites; Cancer; Cell Biology/Gene Expression; Cell Biology/Leukocyte Signaling and Gene Expression; Cell cycle; Cell division; Cell growth; Cell immortalization; Cell Line, Tumor; Chromatin; Chromatin Assembly and Disassembly; Chromatin remodeling; Cytokines; Deoxyribonucleic acid; DNA; DNA repair; EBNA-1 protein; Enrichment; Epstein-Barr virus; Epstein-Barr Virus Nuclear Antigens - genetics; Gene Expression; Gene Expression Profiling; Gene rearrangement; Genes; Genetic transformation; Genomes; Growth factors; Herpesvirus 4, Human; Humans; Immortalization; Lymphocytes B; Lymphoma; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - pathology; Lymphoma, B-Cell - virology; Lymphomas; Medicin och hälsovetenskap; Molecular biology; Mutation; Nucleosomes - genetics; Phosphorylation; Promoter Regions, Genetic - genetics; Proteins - metabolism; Transcription; Transcription (Genetics); Transcription factors; Transfection; Transformation; Virology/Effects of Virus Infection on Host Gene Expression; Viruses; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0012052

The Epstein-Barr virus (EBV) encoded nuclear antigen (EBNA)-1 regulates virus replication and transcription, and participates in the remodeling of the cellular environment that accompanies EBV induced B-cell immortalization and malignant transformation. The putative cellular targets of these effects of EBNA-1 are largely unknown. To address this issue we have profiled the transcriptional changes induced by short- and long-term expression of EBNA-1 in the EBV negative B-cell lymphoma BJAB. Three hundred and nineteen cellular genes were regulated in a conditional transfectant shortly after EBNA-1 induction while a ten fold higher number of genes was regulated upon continuous EBNA-1 expression. Promoter analysis of the differentially regulated genes demonstrated a significant enrichment of putative EBNA-1 binding sites suggesting that EBNA-1 may directly influence the transcription of a subset of genes. Gene ontology analysis of forty seven genes that were consistently regulated independently on the time of EBNA-1 expression revealed an unexpected enrichment of genes involved in the maintenance of chromatin architecture. The interaction network of the affected gene products suggests that EBNA-1 may promote a broad rearrangement of the cellular transcription landscape by altering the expression of key components of chromatin remodeling complexes.