Detecting elevated H3K27me3 in colon tumor samples.

(A) Comparing distributions of counts for H3K27me3 in tumor (left) and normal (right) colon tissue. Tumor tissue appears to have globally elevated H3K27me3, as shown by the heavier tail in the histogram of counts, corresponding to a greater number of non-zero PBS values (inset). (B) Schematic describing a PBS-based differential analysis of two datasets. The output of the differential analysis is a histogram of the differences in PBS between the two datasets, as shown at the bottom. (C) Histograms summarizing a PBS-based differential analysis of H3K27me3 PBS between tumor and normal colon tissue. Plots are facetted based on overlap with a region of hypomethylated DNA (hypomethylated block). (D) Histograms describing a PBS-based differential analysis of H3K27me3 between tumor and normal colon tissue in hypomethylated blocks (right-hand facet in (C)). Plots are facetted based on overlap with euchromatin or heterochromatin, as defined by Hi-C. The increase in H3K27me3 in tumor tissue is more pronounced in regions of euchromatin that overlap hypomethylated tumor DNA. Hypomethylated tumor DNA is defined as a 5 kB bin with methylation levels lower than those of normal tissue [24].