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.