Transcription profiling of Epstein-Barr virus nuclear antigen (EBNA)-1 expressing cells suggests targeting of chromatin remodeling complexes.
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.
Sompallae
Ramakrishna
R
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Callegari
Simone
S
Kamranvar
Siamak Akbari
SA
Masucci
Maria G
MG
D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D015870:Gene Expression; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology / Q000821:virology; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D014162:Transfection
D019309:Epstein-Barr Virus Nuclear Antigens; D009707:Nucleosomes; D011506:Proteins; C417029:EBV-encoded nuclear antigen 1