Carcinogenesis, Vol. 21, No. 3, 461-467,
March 2000
© 2000 Oxford University Press
Cancer Biology |
DNA methylation: past, present and future directions
University of Southern California, Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, MS 83, Los Angeles, CA 90033, USA
DNA methylation, or the covalent addition of a methyl group to cytosine within the context of the CpG dinucleotide, has profound effects on the mammalian genome. These effects include transcriptional repression via inhibition of transcription factor binding or the recruitment of methyl-binding proteins and their associated chromatin remodeling factors, X chromosome inactivation, imprinting and the suppression of parasitic DNA sequences. DNA methylation is also essential for proper embryonic development; however, its presence can add an additional burden to the genome. Normal methylation patterns are frequently disrupted in tumor cells with global hypomethylation accompanying region-specific hypermethylation. When these hypermethylation events occur within the promoter of a tumor suppressor gene they will silence the gene and provide the cell with a growth advantage in a manner akin to deletions or mutations. Recent work indicating that DNA methylation is an important player in both DNA repair and genome stability as well as the discovery of a new family of DNA methyltransferases makes now a very exciting period for the methylation field. This review will highlight the major findings in the methylation field over the past 20 years then summarize the most important and interesting future directions the field is likely to take in the next millennium.
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J. W. Crott, S. T. Mashiyama, B. N. Ames, and M. F. Fenech Methylenetetrahydrofolate reductase C677T polymorphism does not alter folic acid deficiency-induced uracil incorporation into primary human lymphocyte DNA in vitro Carcinogenesis, July 1, 2001; 22(7): 1019 - 1025. [Abstract] [Full Text] [PDF]
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D. J. Smiraglia, L. J. Rush, M. C. Fruhwald, Z. Dai, W. A. Held, J. F. Costello, J. C. Lang, C. Eng, B. Li, F. A. Wright, et al. Excessive CpG island hypermethylation in cancer cell lines versus primary human malignancies Hum. Mol. Genet., June 1, 2001; 10(13): 1413 - 1419. [Abstract] [Full Text] [PDF]
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S. Derreumaux, M. Chaoui, G. Tevanian, and S. Fermandjian Impact of CpG methylation on structure, dynamics and solvation of cAMP DNA responsive element Nucleic Acids Res., June 1, 2001; 29(11): 2314 - 2326. [Abstract] [Full Text] [PDF]
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 G. Macintyre, C. V. Atwood, and C. G. Cupples Lowering S-Adenosylmethionine Levels in Escherichia coli Modulates C-to-T Transition Mutations J. Bacteriol., February 1, 2001; 183(3): 921 - 927. [Abstract] [Full Text]
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R. A Jacob Folate, DNA methylation, and gene expression: factors of nature and nurture Am. J. Clinical Nutrition, October 1, 2000; 72(4): 903 - 904. [Full Text] [PDF]
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A. Balmain and C. C.Harris Carcinogenesis in mouse and human cells: parallels and paradoxes Carcinogenesis, March 1, 2000; 21(3): 371 - 377. [Abstract] [Full Text] [PDF]
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G. Vilkaitis, A. Dong, E. Weinhold, X. Cheng, and S. Klimasauskas Functional Roles of the Conserved Threonine 250 in the Target Recognition Domain of HhaI DNA Methyltransferase J. Biol. Chem., December 1, 2000; 275(49): 38722 - 38730. [Abstract] [Full Text] [PDF]
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S. Ammanamanchi and M. G. Brattain 5-AzaC Treatment Enhances Expression of Transforming Growth Factor-beta Receptors through Down-regulation of Sp3 J. Biol. Chem., August 24, 2001; 276(35): 32854 - 32859. [Abstract] [Full Text] [PDF]
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Y. Yatabe, S. Tavare, and D. Shibata From the Cover: Investigating stem cells in human colon by using methylation patterns PNAS, September 11, 2001; 98(19): 10839 - 10844. [Abstract] [Full Text] [PDF]
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O. Galm, M. R. Rountree, K. E. Bachman, K.-W. Jair, S. B. Baylin, and J. G. Herman Enzymatic Regional Methylation Assay: A Novel Method to Quantify Regional CpG Methylation Density Genome Res., January 1, 2002; 12(1): 153 - 157. [Abstract] [Full Text] [PDF]
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