The role of DNA methylation in mammalian epigenetics

Genes constitute only a small proportion of the total mammalian genome, and the precise control of their expression in the presence of an overwhelming background of noncoding DNA presents a substantial problem for their regul ation. Noncoding DNA, containing introns, repetitive elements, and potentia lly active transposable elements, requires effective mechanisms for its ton g-term silencing. Mammals appear to have taken advantage of the possibiliti es afforded by cytosine methylation to provide a heritable mechanism for al tering DNA-protein interactions to assist in such silencing. Genes can be t ranscribed from methylation-free promoters even though adjacent transcribed and nontranscribed regions are extensively methylated. Gene promoters can be used and regulated white keeping noncoding DNA, including transposable e lements, suppressed. Methylation is also used for Long-term epigenetic sile ncing of X-linked and imprinted genes and can either increase or decrease t he level of transcription, depending on whether the methylation inactivates a positive or negative regulatory element.