1. Distribution of CpG dinucleotide in the human genome and differences in methylation patterns between normal and tumor cells. In the majority of the mammalian genome, depicted as exons 2 and 3 of a sample gene (numbered boxes), introns of the gene (line between the exons), and regions outside the gene, the CpG dinucleotide has been depleted over evolution as shown by the sparse number of such sites (lollipops). Small regions of DNA, approximately kb in size, harbor the expected number of CpG sites and are termed CpG islands. Many of these are associated with promoter regions of approximately half of the genes in the genome (frequent lollipops surrounding exon 1 of the sample gene). In normal cells, most CpG sites outside CpG islands are methylated (yellow lollipops) while most gene promoter CpG island sites are unmethylated (open lollipops). This unmethylated state of the promoter CpG islands is a permissive state for active gene transcription (arrow, top panel). In cancer cells, the DNA methylation and chromatin patterns are shifted. Many CpG sites in the bulk genome and coding region of genes that should be methylated become unmethylated, and a growing list of genes have abnormal methylation of CpG island-containing promoters with associated transcriptional silencing (X at transcription start site).
Source: DNA Methylation and Epigenetic Silencing of Genes in Cancer, The Online Metabolic and Molecular Bases of Inherited Disease
Citation: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. The Online Metabolic and Molecular Bases of Inherited Disease; 2014 Available at: Accessed: October 21, 2017
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