DNA methylation patterns in normal and cancer cells. (A) In normal cells, most CpGs located outside of promoters in gene bodies and intergenic regions are methylated (red circles), whereas promoter-associated CpG islands are protected from DNA methylation (white circles). (B) In cancer cells, a global or localized loss of 5-methylcytosine occurs at gene bodies and intergenic regions, whereas CpG-rich regions like promoters are usually heavily methylated, which might lead to transcriptional repression. Regions of intermediate CpG levels such as shores are associated with tissue-specific methylation. Global loss (left plot) and focal gain (right plot) of DNA methylation are depicted as tracks of the University of California Santa Cruz genome browser  using whole-genome bisulfite sequencing data for normal and cancer cell lines. Tracks for CpG islands and selected histone modifications, including H3K4me3, which is associated with transcriptionally active promoters, and H3K4me1 and H3K27ac as markers for enhancers, are illustrated below the gene track. Each color of the histone tracks represents an individual ENCODE cell line. The deleted in colon cancer gene (DCC) was taken as an exemplary locus for which long-range hypomethylation regions (horizontal blue bars) are observed in the breast cancer cell line HCC1954 and in the liver carcinoma cell line HepG2, but not in normal mammary epithelial cells (HMEC) or the myofibroblast cell line IMR90. The glutathione S- transferase P1 gene (GTSP1) represents an example of promoter hypermethylation (highlighted in red) in cancer cell lines compared to normal cells. TSS, transcription start site.