Epigenetic silencing of tumor suppressor genes during in vitro Epstein-Barr virus infection.
DNA-methylation at CpG islands is one of the prevalent epigenetic alterations regulating gene-expression patterns in mammalian cells. Hypo- or hypermethylation-mediated oncogene activation, or tumor suppressor gene (TSG) silencing mechanisms, widely contribute to the development of multiple human cancers. Furthermore, oncogenic viruses, including Epstein-Barr virus (EBV)-associated human cancers, were also shown to be influenced by epigenetic modifications on the viral and cellular genomes in the infected cells. We investigated EBV infection of resting B lymphocytes, which leads to continuously proliferating lymphoblastoid cell lines through examination of the expression pattern of a comprehensive panel of TSGs and the epigenetic modifications, particularly methylation of their regulatory sequences. EBV infection of primary B lymphocytes resulted in global transcriptional repression of TSGs through engagement of hypermethylation. Therefore, CpG methylation profiles of TSGs may be used as a prognostic marker as well as development of potential therapeutic strategies for controlling acute infection and EBV-associated B-cell lymphomas.
Department of Microbiology and Tumor Virology Program of the Abramson Comprehensive Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
Abhik
A
Saha
Department of Microbiology and Tumor Virology Program of the Abramson Comprehensive Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
Hem C
HC
Jha
Department of Microbiology and Tumor Virology Program of the Abramson Comprehensive Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
Santosh K
SK
Upadhyay
Department of Microbiology and Tumor Virology Program of the Abramson Comprehensive Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 erle@upenn.edu.
Erle S
ES
Robertson
D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D049109:Cell Proliferation; D002470:Cell Survival; D002843:Chromatin; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000276:immunology; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008214:Lymphocytes / Q000166:cytology; D009369:Neoplasms / Q000235:genetics / Q000821:virology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic; D017735:Virus Latency
D002843:Chromatin
B-cell lymphoma; EBV; lymphoblastoid cell lines; promoter methylation; tumor suppressor genes