Figure 2.

A schematic diagram shows the impact of EBV on epigenetic dysregulation in EBVaGC. LMP2A inhibits TET2 and activates STAT3 and ERK signaling pathways to enhance expression of DNMTs, resulting in promoter DNA hypermethylation to suppress gene expression including PTEN and AQP3. EBNA1 enhanced the expression of ATF3, which functions as a transcription factor, to promote target gene expression, characterized by gain of H3K27ac. EBV can also interact with the host genome, where A-T content is enriched as well as H3K4me1 and H3K27ac, and reduced H3K9me3 levels to promote gene expression.