Altered enhancer methylation predicts changes in the expression profiles of cancer genes. (A) Each of the x-y scatters shows the difference in gene expression between normal and cancer cells as a function of the difference in methylation levels (for example, a difference of +100 indicates that the given site was 0% methylated in the normal cells and 100% methylated in the cancer). The plots on the left are for high-scoring enhancer sites associate with 486 genes,the right plots show the promoters of 394(out of 486) genes that were associated with enhancers, and theplots in the middle show all promoters.Blue dots and clouds donate the frequencies of methylation-versus-expression differences. Linear regression (red lines) and Pearson coefficients (R values) are shown for each scatter. (B) Same as in A, but for the 505methylation sites (out of the 1,911) in state 4 enhancers. (C)Left:Overlap between the genes (score ≥0.85) in the upper-left quadrants (that is, genes thatwere upregulated by ≥0.25 expression units withdistal enhancers that were hypomethylated by ≥25%) in breast, lung, and the collection of 18 normal versus cancer cell types. The numbers of overlapping genes are indicated. Right: Examples of GO groups that significantly enriched among the 207 genes that were upregulated and hypomethylated in the various cancer types (the entire list is provided in Table S4 in Additional file 1).