DNA methylation plays an important role in chromatin organization and gene expression.
It is part of an epigenetic code that is maintained and inherited throughout cellular divisions and generally serves as a mechanism for the repression of gene expression. DNA methylation is maintained by DNA methyltransferases which catalyze the addition of a methyl group donated by S-adenosyl-methione to 5’ cytosines located in the context of a CpG dinucleotide. Cytosines in CpG poor regions are usually methylated whereas those in CpG rich areas, known as CpG islands, are generally hypomethylated. Hypomethylation allows for an open chromatin structure and is usually present in the promoter regions of active genes while methylation of CpGs results in a closed chromatin structure and is found in silenced intergenic and intronic regions. The mechanism of silencing by DNA methylation is not well understood. It is proposed that methylation silences gene expression by impeding the binding of transcription factors to gene promoters. Additionally it is proposed that silencing might be achieved by methyl-binding proteins (MBDs) that recruit chromatin modifying factors (e.g. histone deacetylases) that compact and inactivate chromatin.
Proper DNA methylation is critical to the cellular processes of X-inactivation, imprinting, the silencing of repetitive elements, and development. This is evidenced by the finding that epigenetic errors and aberrant DNA methylation are the cause of multiple imprinting syndromes, pediatric syndromes, neuropsychiatric disorders, immune disorders, and cancers. A full understanding of the mechanisms of DNA methylation will promote the development of therapies for the prevention and treatment of diseases caused by aberrant DNA methylation.
1. Miranda, T. B. & Jones, P. A. (2007). DNA methylation: the nuts and bolts of repression. J.Cell Physiol., 213, 384-390.
2. Rodenhiser, D. & Mann, M. (2006). Epigenetics and human disease: translating basic biology into clinical applications. Canadian Medical Association Journal, 174, 341-348.
Bethyl Laboratories Portfolio of Antibodies for the Study of DNA Methylation
Antibodies to Jumonji Proteins (Demethylases)