Saha Abhik, Jha Hem C, Upadhyay Santosh K, Robertson Erle S
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.
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
Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):E5199-207. doi: 10.1073/pnas.1503806112. Epub 2015 Aug 31.
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.
CpG岛的DNA甲基化是调节哺乳动物细胞基因表达模式的常见表观遗传改变之一。低甲基化或高甲基化介导的癌基因激活，或肿瘤抑制基因（TSG）沉默机制，在多种人类癌症的发生发展中起着广泛作用。此外，致癌病毒，包括与爱泼斯坦-巴尔病毒（EBV）相关的人类癌症，也被证明会受到感染细胞中病毒和细胞基因组表观遗传修饰的影响。我们通过检测一组全面的TSG的表达模式及其表观遗传修饰，特别是其调控序列的甲基化，研究了静息B淋巴细胞的EBV感染，这种感染会导致持续增殖的淋巴母细胞系。原发性B淋巴细胞的EBV感染通过高甲基化作用导致TSG的整体转录抑制。因此，TSG的CpG甲基化谱可作为一种预后标志物，也可用于开发控制急性感染和EBV相关B细胞淋巴瘤的潜在治疗策略。
