Epigenomic research has demonstrated that stable, reversible alteration of gene expression is mediated by patterns of methylation of cytosines of DNA and of chromatin remodeling resulting from histone modification, the binding of nuclear proteins to chromatin, and interactions between these networks. Many of the basic principles and complexities that underlie epigenetic phenomena have been identified, but the molecular mechanisms by which the DNA methylation patterns and histone modifications are established and maintained are not entirely clear. Nevertheless, rapid progress has been made in the mapping and characterization of DNA methylation patterns and histone modifications, and some of the methodologies that have been used for these purposes are described be-low.199,200 Emphasis is placed on newer, automatable techniques that can measure the expression of thousands of genes simultaneously as is needed to establish the diagnostic, prognostic, and therapeutic importance of DNA methylation and histone modifications of emergent candidate genes for cancer and other human disorders.
Older, established methods for measuring the methylation state of DNA include routine chromatographic methods, electromigration methods, and immu-noassays.201 Some of the newer methods reported include semiautomatic detection of methylation at CpG islands,202 oligonucleotide-based microassays,
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