Figure 3
Figure 3. Integrative analysis of gene expression and H3K27me3 profiles. (A) Overall percentage of H3K27me3 alterations (Coc analysis FC > ±1.5 in ATL samples with >100% proviral load vs normal CD4+ T cells) in downregulated genes (expression profile FC < −1.5 in acute-type ATL vs normal CD4+ T cells, P < .001) in ATL cells. (B) Scatter plot showing gene expression changes (x-axis, P < .001) and their relative H3K27me3 changes (y-axis, averaged values from normalized probes) in ATL cells compared with normal CD4+ T cells. (C) Box plots showing relative expression levels of genes (ATL vs normal CD4+ T cells, P < .001) with H3K27me3 gain (Coc FC > 1.5 in ATL) and loss (Coc FC < −1.5 in ATL) in acute-type ATL and normal CD4+ T cells (*P < .001). (D) Box plot showing relative expression levels of H3K27me3-associated silenced gene set in ATL cells with each clinical subtype compared with normal CD4+ T cells (*P < 1E−10). (E) Venn diagram showing H3K27me3-associated (Coc FC > 1) suppressed gene set (expression FC < −1.5, P < .05) during clinical progression of ATL. (F) Gene ontology analysis of H3K27me3-associated suppressed 856 genes (defined in supplemental Figure 4). P values (left) and gene counts (right, clinical subtypes are indicated by color) of the top 10 categories are shown. (G) Epigenetic reprogramming of KDM family genes in ATL. The heat map and middle graph show expression patterns of KDM family in acute-type ATL cells and normal CD4+ T cells. H3K27me3 alterations are shown in the right graph. (H) Venn diagram showing miRNAs downregulated in ATL (white circle, miRNA array FC < −1.5, P < .05) and those associated with H3K27me3 gain in ATL cells compared with normal CD4+ T cells (gray circle, Coc FC > 1). (I) Sequence motif analysis at miRNA gene regions epigenetically downregulated in ATL. Top 5 transcription factors and Fisher scores are provided. (J) Relative expression levels of H3K27me3-associated suppressed 75 miRNAs defined in (H) (*P < .0001). (K) ATL-specific epigenetic reprogramming of HOXA cluster. Top, expression levels of HOXA genes in ATL cells relative to normal CD4+ T cells (solid bars indicate P < .05). Bottom, relative H3K27me3 levels at HOXA loci in primary ATL cells, TL-Om1 cells, and normal CD4+ T cells.

Integrative analysis of gene expression and H3K27me3 profiles. (A) Overall percentage of H3K27me3 alterations (Coc analysis FC > ±1.5 in ATL samples with >100% proviral load vs normal CD4+ T cells) in downregulated genes (expression profile FC < −1.5 in acute-type ATL vs normal CD4+ T cells, P < .001) in ATL cells. (B) Scatter plot showing gene expression changes (x-axis, P < .001) and their relative H3K27me3 changes (y-axis, averaged values from normalized probes) in ATL cells compared with normal CD4+ T cells. (C) Box plots showing relative expression levels of genes (ATL vs normal CD4+ T cells, P < .001) with H3K27me3 gain (Coc FC > 1.5 in ATL) and loss (Coc FC < −1.5 in ATL) in acute-type ATL and normal CD4+ T cells (*P < .001). (D) Box plot showing relative expression levels of H3K27me3-associated silenced gene set in ATL cells with each clinical subtype compared with normal CD4+ T cells (*P < 1E−10). (E) Venn diagram showing H3K27me3-associated (Coc FC > 1) suppressed gene set (expression FC < −1.5, P < .05) during clinical progression of ATL. (F) Gene ontology analysis of H3K27me3-associated suppressed 856 genes (defined in supplemental Figure 4). P values (left) and gene counts (right, clinical subtypes are indicated by color) of the top 10 categories are shown. (G) Epigenetic reprogramming of KDM family genes in ATL. The heat map and middle graph show expression patterns of KDM family in acute-type ATL cells and normal CD4+ T cells. H3K27me3 alterations are shown in the right graph. (H) Venn diagram showing miRNAs downregulated in ATL (white circle, miRNA array FC < −1.5, P < .05) and those associated with H3K27me3 gain in ATL cells compared with normal CD4+ T cells (gray circle, Coc FC > 1). (I) Sequence motif analysis at miRNA gene regions epigenetically downregulated in ATL. Top 5 transcription factors and Fisher scores are provided. (J) Relative expression levels of H3K27me3-associated suppressed 75 miRNAs defined in (H) (*P < .0001). (K) ATL-specific epigenetic reprogramming of HOXA cluster. Top, expression levels of HOXA genes in ATL cells relative to normal CD4+ T cells (solid bars indicate P < .05). Bottom, relative H3K27me3 levels at HOXA loci in primary ATL cells, TL-Om1 cells, and normal CD4+ T cells.

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