Genome-wide analysis of histone modification alteration at enhancer regions during epstein-barr virus infection.

We analysed epigenetic alterations by EBV infection especially at enhancer regions, to elucidate their contribution to tumorigenesis. We performed ChIP-seq on H3K4me3, H3K4me1, H3K27ac, H3K27me3 and H3K9me3 using gastric epithelial cells with or without EBV infection. We showed that repressive marks were redistributed after EBV infection, resulting in aberrant enhancer activation and repression. Enhancer dysfunction leads to activation of pathway related to cancer hallmarks (e.g. resisting cell death, disrupting cellular energetics, activation invasion, evading growth suppressors, sustaining proliferative signaling, angiogenesis and tumor promoting inflammation) and inactivation of tumour suppressive pathway. Dysregulation of cancer-related genes during in vitro EBV infection were also observed in EBV+ gastric cancer patients. Our analysis showed that EBV-infection associated epigenetic alteration may contribute to tumorigenesis through enhancer activation and repression. Overall design: Examination of open chromatin regions and 2 different histone modifications in EBV infected or uninfected gastric cancer cells.