Integrative analysis of the epigenome and transcriptome. (A) Integrative scatterplots contrasting expression differences with DNA methylation differences in CIMP-positive (left) and CIMP-negative (right) CAEBV compared with the normal control. Genes and probes associated with the promoter showing significant differences in gene expression (|log₂FC| ≥1.5 and adjusted [adj] P < .05) and DNA methylation (|ΔM| ≥2 and adj P < .05) are highlighted. Tumor suppressor genes and antiherpesvirus genes are highlighted in green and blue, respectively. (B) Pathway analysis of DNA hypermethylated silenced genes in CIMP-positive CAEBV (highlighted in the lower right corner in panel A) performed using Metascape software. (C) LOLA enrichment analysis of 100 differentially hypermethylated regions in promoters. Significantly enriched categories from CISTROME or ENCODE entries of the LOLA Core databases are shown. (D) Expression of EZH2 in NK cells from CIMP-positive, CIMP-negative, EBV-IM, and control cases (healthy volunteers and non-EBV–IM-like). Box plots show median (lines), interquartile ranges (IQRs) (boxes), and ±1.5 × IQR (whiskers). Significance was assessed using the Dunnett T3 test for multiple comparisons against controls. (E) CUT&RUN profile differences in CIMP-positive (S_C_10 NK_LCL) (top) and CIMP-negative (T_H_01 NK_LCL) (bottom) samples compared with the normal control (Control 1 NK cell) for H3K27me3 (left) and H3K4me3 (right) over the average gene body for all genes or hypermethylated and silenced genes in CIMP-positive CAEBV. GO, gene ontology; Log₂FC, log₂ fold change; TES, transcription end site; TPM, transcripts per million; TSS, transcription start site.