ABSTRACT
In DNA isolated from normal healthy tissues, about 3.5%–4% of cytosines are methylated [1,2]. Methylation in the genome is not distributed evenly-promoters and CpG islands are preferentially found in the unmethylated compartment, as to a lesser extent are phylogenetically conserved sequences of unidentified function [3]. The methylated domain of the genome comprises satellite and interspersed repeat sequences, intragenic sequences (excluding the first exon), and unannotated single-copy sequence; however, some promoters and CpG islands (biased toward shorter ones) were identified in the methylated DNA fraction of brain DNA [3]. Genome scanning approaches [4,5] have identified that the promoters of a number of genes are methylated in a tissue-specific manner and that lack of methylation correlated with expression of associated genes. Disruption of epigenetic regulation in cancer involves both hypermethylation of specific sequences [considered in Chapters 3 and 6] and hypomethylation of other sequences and regions. The methylated compartment of the genome that may become hypomethylated thus includes all classes of repeated sequence, intragenic and single-copy intergenic sequences, the inactive X chromosome, and imprinted regions, as well as a subset of promoters or CpG islands that show tissue-specific methylation. The specific case of imprinted genes is reviewed in Chapter 4.
