Figure 1: Epigenetic alterations at enhancers distinguish CRC from normal colon.
From: Hotspots of aberrant enhancer activity punctuate the colorectal cancer epigenome
(a) Normalized H3K27ac ChIP-seq tracks of all CRC cell line, colon crypt, and tumour samples at a representative locus (hg19, chr1:201,960,000–202,129,000). Super-tracks (red) correspond to median binned signal of all normal crypts or all CRC cell lines. Each track is labelled with the sample type and name. (b) Average number of H3K27ac ChIP-seq peaks that overlap promoters (≤2 kb from TSS; grey) and putative enhancers (>2 kb from TSS; white). Dots represent counts in each of the 31 CRC cell lines and four normal colon samples, bars represent mean±s.d. (c) Relative enrichment of H3K27ac ChIP-seq signal in a representative CRC cell line (V410) compared with normal colon crypts. Peaks differentially enriched between normal and CRC (Benjamini–Hochberg corrected P<0.05) are shown in red and blue. (d) H3K27ac and H3K4me1 ChIP-seq and DHS tracks at exemplar gained (left) and lost (right) VELs in a representative CRC cell line (V410; blue) compared with a normal colon sample (black). (e) Fold change of expression of all genes associated with gained (red) and lost (blue) VELs, and genes not associated with VELs (nonVEL; grey). **MWW P<1 × 10−99 versus non-VEL genes. Box boundaries represent 1st and 3rd quartiles, middle line represents median, and whiskers extend to the nearer of the data extremes or 1.5 times the IQR. (f) Percentage of lost (blue), gained (red), and unchanged (grey) enhancers detected in each CRC cell line. (g) Unsupervised clustering of all pairwise correlations of enhancer RPKMs for CRC cell lines and normal colon samples. Colour bars (middle) indicate clinical and molecular characteristics of each sample. Green boxes indicate samples that are more (solid line) and less (dashed line) similar to one another and to crypts. A,ad, adenoma; B–D, Dukes stage B–D; M,met, metastasis; N,NL, normal; U, unknown; P, primary tumour; AA, African American; C, Caucasian; M, male; F, female; R, right; L, left; MSI, microsatellite instable; MSS, microsatellite stable.
