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DNA Methylation

DNA methylation is the addition of a methyl group to the carbon-5 position of cytosine residues. It is the only common covalent modification of human DNA and occurs almost exclusively at cytosines that are followed immediately by guanine.

DNA methylation results from the activity of a family of DNA methyltransferase (DNMT) enzymes that catalyze the addition of a methyl group to the cytosine residues at CpG dinucleotides (Bird, 1996). These so-called CpG dinucleotides include approximately 3-5% of all the cytosine residues within the human genome (Ehrlich et al., 1982).

The bulk of the human genome displays a clear depletion of CpG dinucleotides. This is believed to be due to the high rate of deamination of 5-methylcytosine. Those CpG dinucleotides that are present are nearly always methylated.

By contrast, seventy to eighty percent of these CpG dinucleotides are located in clusters termed CpG islands, which are up to a few kilobases in length and are nearly always free of methylation, unlike the bulk of DNA (Jones and Baylin, 2002).

The exception to this pattern of methylation is on the inactive X chromosome in females (Antequera and Bird, 1993). The genome consists of ~45,000 CpG islands and 50-60% of these are further clustered within control regions of a gene, mainly in the regulatory and promoter regions, but often in other parts of the gene, including exons (Bird, 1986). This pattern of DNA methylation is stably inherited from one cell generation to the next (Gardiner-Garden and Frommer, 1987).

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