Figure 4. Hypermethylated CGIs fall within long, tumor-specific PMDs.

(a) Density plot of average DNA methylation within all 20-kb windows on chromosome 4 showing a distinct subset of windows representing PMDs in the tumor but not normal colon tissue. (b) We identified PMDs for four cell types by searching for 100-kb partially methylated windows (see text), and we compared the percentage of the genome contained within PMDs between the tumor and normal colon tissue along with two other cell types⁷. (c) The average methylation change is shown as a function of distance from CGI promoters for all promoters that were unmethylated in the normal colon (with mean methylation <0.2). We divided promoters into methylation-prone (MP; with mean tumor methylation >0.3) and methylation-resistant (MR; with mean tumor methylation <0.2), and the plots are oriented to show the transcribed region toward the right side. (d) UCSC Genome Browser plot of a representative 10-Mb region on chromosome 3q showing substantial overlap between colon tumor and IMR-90 PMDs, Lamin-B1 marks and focal hypermethylation (methylation-resistant elements are visible as red spikes in the methylation change track). Lamin-B1 and ENCODE enhancer and promoter tracks are from the UCSC annotation database.