Alterations of DNA methylation and CTCF binding by EBV infection of gastric epithelial cells

Epstein-Barr virus-associated gastric cancer (EBVaGC) represents approximately 7-10% of all gastric cancers and displays drastic hypermethylation compared to other gastric cancer subtypes. EBV infection of gastric epithelial cells induces hypermethylation of both the host and viral genomes. However, the role of EBV-mediated hypermethylation in regulating CTCF binding, chromosome topology, and enhancer-promoter interactions and their role in gastric cancer development remains unknown. We infected tumor and nontumor gastric cell lines with EBV, which we followed by assessments of genome-wide DNA methylation, CTCF binding, and gene expression changes to address these questions systematically. We detected changes in methylation of hundreds of CTCF binding sites, as well as gain and loss of CTCF binding at multiple binding sites. This suggest that EBV infection has a drastic effect on the chromosomal topology of gastric cells, that may play a role in supporting the progression of EBV associated gastric cancer.