DNA methylation: past, present and future directions

DNA methylation, or the covalent addition of a methyl group to cytosine wit hin the context of the CpG dinucleotide, has profound effects on the mammal ian genome. These effects include transcriptional repression via inhibition of transcription factor binding or the recruitment of methyl-binding prote ins and their associated chromatin remodeling factors, X chromosome inactiv ation, imprinting and the suppression of parasitic DNA sequences. DNA methy lation is also essential for proper embryonic development; however, its pre sence can add an additional burden to the genome. Normal methylation patter ns are frequently disrupted in tumor cells with global hypomethylation acco mpanying region-specific hypermethylation. When these hypermethylation even ts occur within the promoter of a tumor suppressor gene they will silence t he gene and provide the cell with a growth advantage in a manner akin to de letions or mutations. Recent work indicating that DNA methylation is an imp ortant player in both DNA repair and genome stability as well as the discov ery of a new family of DNA methyltransferases makes now a very exciting per iod for the methylation field. This review will highlight the major finding s in the methylation field over the past 20 years then summarize the most i mportant and interesting future directions the field is likely to take in t he next millennium.