Fig. 3

EZH2 noncanonically occupies promoters associated with metabolic genes

(A-B) Averaged signal intensities (A) and heatmaps (B) for EZH2, H3K27me3 and SUZ12 ± 2 kb from the centres of EZH2 or H3K27me3 peaks in OVCAR8 cells

(C) Venn diagram showing the significant overlap between EZH2 and H3K27me3 binding sites identified in OVCAR8 cells

(D) Pie-chart plot showing the genomic distribution of peaks with EZH2-solo binding in OVCAR8 cells

(E-F) Averaged signal intensities (E) and heatmaps (F) for EZH2, H3K27me3, SUZ12 and H3K4me3 ± 2 kb from the centres of EZH2-solo, EZH2-ensemble or H3K27me3-solo peaks in OVCAR8 cells

(G) Scatterplot showing log2 fold change of genes expression in OVCAR8 cells after DZNep treatment or doxycycline-induced EZH2 silencing. Significant differential expression genes (DEGs) upon either treatments are indicated in blue color, upregulated DEGs in both groups are indicated in orange color, downregulated DEGs in both groups are indicated in green color. Spearman correlation between all genes is shown as a black line (R = 0.846, p < 0.0001)

(H) Venn diagram showing the significant overlap between 617 EZH2 potential targets and EZH2-solo peaks associated genes in OVCAR8 cells. Averaged signal intensities for EZH2, H3K27me3, SUZ12 and H3K4me3 ± 2 kb from the TSS of overlap genes are shown

(I) Gene set enrichment analysis for the 251 EZH2 solo targets using the KEGG and Reactome gene sets. Metabolism-related pathways are among the most enriched (left). The -log10(P-value) of metabolism-related pathways are shown (right)

(J) Metabolism-related genes are upregulated in ovarian cancer tissues, and down regulated after EZH2 reduction. A heatmap showing the relative expression of top 10 metabolic genes in (H) by calculating their Z-score in indicated RNA-Seq data