DNA Methylation and Human Diseases

Genes are switched on and off in tissue specific manner and at specific developmental stages (Jaenisch and Bird, 2003; Ehrlich, 2003; Futscher et al 2002). This transcriptional activity of a given gene is regulated by many factors, among which are that affecting the chromatin structure, like histones modifications and the epigenetic modifications of DNA. The best-known epigenetic modification of DNA is the methyaltion at the 5’ position of cytosines. In mammals this modification of DNA occurs mostly at cytosines in a CpG context. In the recent years a close association was established between the methylation state of a DNA and its transcription activity. Regions that are actively transcribed (Euchromatin) have their promoter regions with mostly unmethylated CpG sites, acetylated histones tail and methylated lysine 4 on H3 subunits, while transcriptionally silent regions (heterochromatin) have mostly methylated CpG sites, deacetylated histones and methylated lysine 9 on H3 subunits (Fig. 1) (Fournier et al 2002; Tamaru and Selker, 2001).