DNA methylation


DNA methylation is the addition of a methyl (CH3) group to either cytosine or adenine in DNA . In cytosine the methyl group is added to carbon 5 of the pyrimidine ring, while in adenine it is added to nitrogen 6 of the purine ring. Both reactions are catalysed by enzymes called DNA methyltransferases. As a phenomenon it is found in a variety of organisms, ranging from mammals including humans, through plants and fungi, to bacteria. In bacteria it serves to protect the genome from the bacteria's own restriction enzymes which degrade invading viral genomes.

Methylated DNA can be detected by restriction enzyme analysis. The restriction enzymes HpaII and MspI both cut at CCGG sites, although HpaII will not cut where DNA methylation has occurred on the second cytosine residue. Different restriction fragments are therefore recovered depending on the methylation state of the DNA.

DNA methylation is crucially important in gene expression and regulation, both during foetal development and throughout the life of an organism. It stabilizes established patterns of gene expression in differentiated cells: for instance, if a muscle cell is expressing certain genes, then DNA methylation silences those genes which should remain unexpressed throughout the lifetime of the muscle cell. DNA methylation also serves to silence lethal genes, such as those integrated into the genome from viruses, and silences proliferative genes to prevent cancer (however, hypermethylation of gene promoters has been linked with carcinogenesis). Methylation is also involved in dosage compensation; for instance via X-chromosome inactivation. It has also been linked to long-term memory storage in humans.

DNA methylation occurs most frequently in CpG sites (CpG, meaning cytosine and guanine residues with a phosphodiester bond in between). However, CpG sites in promoter regions (CpG islands) tend to remain unmethylated. Once a gene is methylated, this methylation is heritable throughout generations of daughter cells. This means that, as well as changes in DNA sequence, changes in transcription state can also be inherited. This is the base of epigenetic phenomena.