PT - JOURNAL ARTICLE AU - Jones, Peter A. AU - Takai, Daiya TI - The Role of DNA Methylation in Mammalian Epigenetics AID - 10.1126/science.1063852 DP - 2001 Aug 10 TA - Science PG - 1068--1070 VI - 293 IP - 5532 4099 - http://science.sciencemag.org/content/293/5532/1068.short 4100 - http://science.sciencemag.org/content/293/5532/1068.full SO - Science2001 Aug 10; 293 AB - 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 regulation. Noncoding DNA, containing introns, repetitive elements, and potentially active transposable elements, requires effective mechanisms for its long-term silencing. Mammals appear to have taken advantage of the possibilities afforded by cytosine methylation to provide a heritable mechanism for altering DNA-protein interactions to assist in such silencing. Genes can be transcribed from methylation-free promoters even though adjacent transcribed and nontranscribed regions are extensively methylated. Gene promoters can be used and regulated while keeping noncoding DNA, including transposable elements, suppressed. Methylation is also used for long-term epigenetic silencing of X-linked and imprinted genes and can either increase or decrease the level of transcription, depending on whether the methylation inactivates a positive or negative regulatory element.