Jones, P.A. & Baylin, S.B. The fundamental role of epigenetic events in cancer. Nat. Rev. Genet. 3, 415–428 (2002).
Esteller, M. & Herman, J.G. Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J. Pathol. 196, 1–7 (2002).
Rountree, M.R., Bachman, K.E., Herman, J.G. & Baylin, S.B. DNA methylation, chromatin inheritance, and cancer. Oncogene 20, 3156–3165 (2001).
Robertson, K.D. DNA methylation, methyltransferases, and cancer. Oncogene 20, 3139–3155 (2001).
Li, E., Bestor, T.H. & Jaenisch, R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69, 915–926 (1992).
Laird, P.W. et al. Suppression of intestinal neoplasia by DNA hypomethylation. Cell 81, 197–205 (1995).
Fournel, M., Sapieha, P., Beaulieu, N., Besterman, J.M. & MacLeod, A.R. Downregulation of human DNA-(cytosine-5) methyltransferase induces cell cycle regulators p16(ink4A) and p21(WAF/Cip1) by distinct mechanisms. J. Biol. Chem. 274, 24250–24256 (1999).
Rhee, I. et al. CpG methylation is maintained in human cancer cells lacking DNMT1. Nature 404, 1003–1007 (2000).
Rhee, I. et al. DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature 416, 552–556 (2002).
Beaulieu, N. et al. An essential role for DNA methyltransferase DNMT3B in cancer cell survival. J. Biol. Chem. 277, 28176–28181 (2002).
Okano, M., Bell, D.W., Haber, D.A. & Li, E. DNA methyltransferases DNMT3a and DNMT3b are essential for de novo methylation and mammalian development. Cell 99, 247–257 (1999).
Li, E., Beard, C. & Jaenisch, R. Role for DNA methylation in genomic imprinting. Nature 366, 362–365 (1993).
Yoder, J.A., Soman, N.S., Verdine, G.L. & Bestor, T.H. DNA (cytosine-5)- methyltransferases in mouse cells and tissues. Studies with a mechanism-based probe. J. Mol. Biol. 270, 385–395 (1997).
Gonzalez-Zulueta, M. et al. Methylation of the 5′ CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing. Cancer Res. 55, 4531–4535 (1995).
Merlo, A. et al. 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat. Med. 1, 633–634 (1995).
Myohanen, S.K., Baylin, S.B. & Herman, J.G. Hypermethylation can selectively silence individual CDKN2A alleles in neoplasia. Cancer Res. 58, 591–593 (1998).
Herman, J.G. et al. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc. Natl. Acad. Sci. USA 95, 6870–6875 (1999).
Kane, M.F. et al. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair–defective human tumor cell lines. Cancer Res. 57, 808–811 (1997).
Leung, S.Y. et al. hMLH1 promoter methylation and lack of hMLH1 expression in sporadic gastric carcinomas with high-frequency microsatellite instability. Cancer Res. 59, 159–164 (1999).
Pogribny, I., Yi, P. & James, S.J. A sensitive new method for rapid detection of abnormal methylation patterns in global DNA and within CpG islands. Biochem. Biophys. Res. Commun. 262, 624–628 (1999).
Jutterman, R., Li, E. & Jaenisch, R. Toxicity of 5-aza-2′-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc. Natl. Acad. Sci. USA 981, 11797 (1994).
Christman, J.K., Schneiderman, N. & Acs, G. Formation of highly stable complexes between 5-azacytosine-substituted DNA and specific non-histone nuclear proteins. Implications for 5-azacytidine-mediated effects on DNA methylation and gene expression. J. Biol. Chem. 260, 4059–4068 (1985).
Haaf, T. & Schmid, M. 5′-Azadeoxycytidine-induced undercondensation in the giant X chromosomes of Microtus agrestis. Chromosoma 98, 93–98 (1989).
Haaf, T. The effects of 5-azacytidine and 5-azadeoxycytidine on chromosome structure and function: implications for methylation-associated cellular processes. Pharmacol. Ther. 65, 19–46 (1995).
Liang, G. et al. Cooperativity between DNA methyltransferases in the maintenance methylation of repetitive elements. Mol. Cell Biol. 22, 480–491 (2002).
Jonkers, J. & Berns, A. Conditional mouse models of sporadic cancer. Nat. Rev. Cancer 2, 251–265 (2002).
Bachman, K.E., Rountree, M.R. & Baylin, S.B. Dnmt3a and Dnmt3b are transcriptional repressors that exhibit unique localization properties to heterochromatin. J. Biol. Chem. 276, 32282–32287 (2001).
Margot, J.B., Cardoso, M.C. & Leonhardt, H. Mammalian DNA methyltransferases show different subnuclear distributions. J. Cell. Biochem. 83, 373–379 (2001).
Herman, J.G., Graff, J.R., Myohanen, S., Nelkin, B.D. & Baylin, S.B. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc. Natl. Acad. Sci. USA 93, 9821–9826 (1996).
Agathanggelou, A. et al. Methylation-associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours. Oncogene 20, 1509–1518 (2001).