Fig. 4

Hypomethylation at cancer-related super-enhancers in colorectal tumors. a Differential DNA methylation (occupancy of hypomethylated regions (HMRs)) at colorectal cancer-related super-enhancers between normal mucosa and primary colorectal cancer samples (WGBS, x-axis). Differentially methylated super-enhancers are indicated (colored dots, δ HMR occupancy >25 %). Results were validated in a cohort of matched normal and primary colorectal tumor samples (TCGA, n = 41, HumanMethylation450 BeadChip) and significant differences assessed by the Wilcoxon test (green dots, p < 0.05, y-axis). b Hypomethylation at super-enhancers was associated with increased target gene expression analyzed by HumanMethylation450 BeadChip (450 K, x-axis) and RNA-seq (y-axis) in matched primary colorectal cancer samples (n = 12, TCGA). Expression data are displayed as log transformed fold-change (log2FC). c DNA methylation profiles of the super-enhancer regions associated with MYC and RNF43 in normal and colorectal cancer samples (WGBS). Smoothed (colored line), raw (gray bars) CpG methylation levels, hypomethylated regions (colored bars) and super-enhancers (black bars) are indicated. The enhancer-related histone marks H3K27ac (orange) and H3K4me1 (blue) and the promoter-related mark H3K4me3 (pink) are displayed as ChIP-seq signal intensities (bottom panels) [11]. The transcription start sites are indicated (broken line). d Gene expression levels of the transcription factor FOXQ1 in normal (blue) and colorectal cancer (red) samples (TCGA). e, f Association of FOXQ1 expression and DNA methylation levels (HumanMethylation450 BeadChip, 450 K) at hypomethylated super-enhancer regions (e) or expression levels of associated target genes (f) in colorectal cancer in normal (blue) and colorectal cancer (red) samples (TCGA). Significance was assessed from a linear regression model applied solely to the cancer samples. RSEM RNA-Sequencing by Expectation Maximization