Epigenetic alterations in primary ATL cells. (A) Overall percentage of genes with H3K27me3 states in ATL cells compared with normal CD4⁺ T cells. The averaged methylation values at each gene (fold change [FC] > ±1.5 vs normal CD4⁺ T cells) were calculated from normalized probes. (B) Methylation intensity profiling of normalized each probe in ATL cells (n = 3) and normal CD4⁺ T cells (n = 2). Relative H3K27me3 levels of each probe (P < .05) are shown in histogram. (C) Heat maps and hierarchical clustering of H3K27me3 (left) and H3K4me3 (right) levels at regions (LogFC > 3) in primary ATL cells, normal T cells, and TL-Om1 cells. (D) The number of probes showing gain (LogFC > 3) or loss (LogFC < −3) of H3K27me3 and H3K4me3 in ATL cells compared with normal CD4⁺ T cells. (E) Venn diagram showing the overlap between genes associated with H3K27me3 in ATL cells (FC > 2 vs normal CD4⁺ T cells), embryonic stem cells,³⁶  and DLBCL cells.³²  (F-G) Composite enrichment profile of H3K27me3 relative to the closest transcriptional start site (TSS). Graphs show relative H3K27me3 levels calculated from all normalized probes (F) and frequency of H3K27me3 gain in ATL compared with normal CD4⁺ T cells (G; closed circles indicate gain in ATL [P < .05]; open circles indicate loss in ATL [P < .05]). (H) Box plots showing relative H3K27me3 levels at silenced promoter region (expression FC < −2 in acute-type ATL vs normal CD4⁺ T cells, P < .001) and gene-enhancer region (defined by H3K4me1+H3K27ac marks in CD4⁺ T cells¹⁴ ) in ATL and normal T cells.