The role of DNA methylation in cancer genetics and epigenetics

Annual Review of Genetics

Volumn 30, Issue , 1996, Pages 441-464

  Laird, Peter W ^a   Jaenisch, Rudolf ^b  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

5 methylcytosine; cancer; DNA methylation; epigenetics; genetics; imprinting; mutation

Indexed keywords

5 METHYLCYTOSINE; DINUCLEOTIDE; DNA; DNA METHYLTRANSFERASE;

CANCER GENETICS; CARCINOGENESIS; DNA METHYLATION; GENOME IMPRINTING; HUMAN; MALIGNANT TRANSFORMATION; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; REVIEW; SILENCER GENE; TUMOR SUPPRESSOR GENE;

ANIMALS; DNA METHYLATION; DNA MODIFICATION METHYLASES; HUMANS; NEOPLASMS;

EID: 0030459140     PISSN: 00664197     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.genet.30.1.441     Document Type: Review

References (201)

1. Antequera F, Bird A. 1993. CpG islands. See Ref. 84a, pp. 169-85
2. Antequera F, Bird A. 1993. Number of CpG islands and genes in human and mouse. Proc. Natl. Acad. Sci. USA 90:11995-99
3. Antequera F, Macleod D, Bird AP. 1989. Specific protection of methylated CpGs in mammalian nuclei. Cell 58:509-17
4. Balmain A. 1995. Cancer. Exploring the bowels of DNA methylation. Curr. Biol. 5:1013-16
5. Bandaru B, Wyszynski M, Bhagwat AS. 1995. HpaII methyltransferase is mutagenic in Escherichia coli. J. Bacteriol. 177:2950-52
6. Barbieri R, Mischiati C, Piva R, Nastruzzi C, Giacomini P, et al 1989. DNA methylation of the Ha-ras-1 oncogene in neoplastic cells. Anticancer Res. 9:1787-91
7. Barbieri R, Piva R, Buzzoni D, Volinia S, Gambari R. 1987. Clustering of undermethylated CCGG and GCGC sequences in the 5′ region of the Ha-ras-1 oncogene of human leukemic K562 cells. Biochem. Biophys. Res. Commun. 145:96-104
8. Barker D, Schafer M, White R. 1984. Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell 36:131-38
9. Barlow DP. 1993. Methylation and imprinting: from host defense to gene regulation? Science 260:309-10
10. Baylin SB, Makos M, Wu JJ, Yen RW, de Bustros A, et al 1991. Abnormal patterns of DNA methylation in human neoplasia: potential consequences for tumor progression. Cancer Cells 3:383-90
11. Bestor T, Laudano A, Mattaliano R, Ingram V. 1988. Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J. Mol. Biol. 203:971-83
12. Bestor TH. 1992. Activation of mammalian DNA methyltransferase by cleavage of a Zn binding regulatory domain. EMBO J. 11:2611-17
13. Bestor TH, Tycko B. 1996. Creation of genomic methylation patterns. Nat. Genet. 12:363-67
14. Bestor TH, Verdine GL. 1994. DNA methyltransferases. Curr. Opin. Cell Biol. 6:380-89
15. Bird A. 1996. The relationship of DNA methylation to cancer. Cancer Surv. In press
16. Bird AP. 1986. CpG-rich islands and the function of DNA methylation. Nature 321:209-13
17. Bird AP. 1995. Gene number, noise reduction and biological complexity. Trends Genet. 11:94-100
18. Brandeis M, Frank D, Keshet I, Siegfried Z, Mendelsohn M, et al. 1994. Sp1 elements protect a CpG island from de novo methylation. Nature 371:435-38
19. Brenton JD, Viville S, Surani MA. 1995. Genomic imprinting and cancer. Cancer Surv. 25:161-71
20. Campoy FJ, Meehan RR, McKay S, Nixon J, Bird A. 1995. Binding of histone H1 to DNA is indifferent to methylation at CpG sequences. J. Biol. Chem. 270:26473-81
21. Carcinogenesis-Testing-Program, NCI. 1978. Bioassay of 5-aza-cytidine for possible carcinogenicity. NCI Carcinog. Tech. Rep. Ser. 42:1-86, CAS No. 320-67-2
22. Carr BI, Reilly JG, Smith SS, Winberg C, Riggs A. 1984. The tumorigenicity of 5-azacytidine in the male Fischer rat. Carcinogenesis 5:1583-90
23. Cedar H. 1988. DNA methylation and gene activity. Cell 53:3-4
24. Cedar H, Stein R, Gruenbaum Y, Naveh MT, Sciaky GN, Razin A. 1983. Effect of DNA methylation on gene expression. Cold Spring Harbor Symp. Quant. Biol. 2:605-9
25. Chandler LA, De CY, Bogenmann E, Jones PA. 1986. Patterns of DNA methylation and gene expression in human tumor cell lines. Cancer Res. 46:2944-49
26. Cheah MS, Wallace CD, Hoffman RM. 1984. Hypomethylation of DNA in human cancer cells: a site-specific change in the c-myc oncogene. J. Natl. Cancer Inst. 73:1057-65
27. Cheng JM, Hiemstra JL, Schneider SS, Naumova A, Cheung NK, et al. 1993. Preferential amplification of the paternal allele of the N-myc gene in human neuroblastomas. Nat. Genet. 4:191-94
28. Cheng X. 1995. Structure and function of DNA methyltransferases. Annu. Rev. Biophys. Biomol. Struct. 24:293-318
29. Christman JK, Sheikhnejad G, Marasco CJ, Sufrin JR. 1995. 5-Methyl-2′-deoxycytidine in single-stranded DNA can act in cis to signal de novo DNA methylation. Proc. Natl. Acad. Sci. USA 92:7347-51
30. Christofori G, Naik P, Hanahan D. 1995. Deregulation of both imprinted and expressed alleles of the insulin-like growth factor 2 gene during beta-cell tumorigenesis. Nat. Genet. 10:196-201
31. Clark SJ, Harrison J, Frommer M. 1995. CpNpG methylation in mammalian cells. Nat. Genet. 10:20-27
32. Cleaver JE, Layher SK. 1995. If the shoe fits: clues on structural recognition of DNA damage. Cell 80:825-27
33. Cooper DN, Youssoufian H. 1988. The CpG dinucleotide and human genetic disease. Hum. Genet. 78:151-55
34. Counts JL, Goodman JI. 1994. Hypomethylation of DNA: an epigenetic mechanism involved in tumor promotion. Mol. Carcinog. 11:185-88
35. Counts JL, Goodman JI. 1995. Alterations in DNA methylation may play a variety of roles in carcinogenesis. Cell 83:13-15
36. Counts JL, Goodman JI. 1995. Hypomethylation of DNA: an epigenetic mechanism that can facilitate the aberrant oncogene expression involved in liver carcinogenesis. In Liver Regeneration and Carcinogenesis, ed. R Jirtle, pp. 227-55. New York: Academic
37. Cravo ML, Mason JB, Dayal Y, Hutchinson M, Smith D, et al. 1992. Folate deficiency enhances the development of colonic neoplasia in dimethylhydrazine-treated rats. Cancer Res. 52:5002-6
38. Diala ES, Cheah MS, Rowitch D, Hoffman RM. 1983. Extent of DNA methylation in human tumor cells. J. Natl. Cancer Inst. 71:755-64
39. Doerfler W. 1983. DNA methylation and gene activity. Annu. Rev. Biochem. 52:93-124
40. Doerfler W. 1991. Patterns of DNA methylation - evolutionary vestiges of foreign DNA inactivation as a host ense mechanism. A proposal. Biol. Chem. Hoppe-Seyler 372:557-64
41. Doerfler W. 1995. The insertion of foreign DNA into mammalian genomes and its consequences: a concept in oncogenesis. Adv. Cancer Res. 66:313-44
42. Driscoll DJ. 1994. Genomic imprinting in humans. Mol. Genet. Med. 4:37-77
43. Dryja TP, Mukai S, Petersen R, Rapaport JM, Walton D, Yandell DW. 1989. Parental origin of mutations of the retinoblastoma gene. Nature 339:556-58
44. Eeles RA. 1995. Germline mutations in the TP53 gene. Cancer Surv. 25:101-24
45. Ehrlich M, Zhang XY, Inamdar NM. 1990. Spontaneous deamination of cytosine and 5-methylcytosine residues in DNA and replacement of 5-methylcytosine residues with cytosine residues. Mutat. Res. 238:277-86
46. El-Deiry WS, Nelkin BD, Celano P, Yen RW, Falco JP, et al 1991. High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer. Proc. Natl. Acad. Sci. USA 88:3470-74
47. Feinberg AP. 1993. Genomic imprinting and gene activation in cancer. Nat. Genet. 4:110-13
48. Feinberg AP, Gehrke CW, Kuo KC, Ehrlich M. 1988. Reduced genomic 5-methylcytosine content in human colonic neoplasia. Cancer Res. 48:1159-61
49. Feinberg AP, Kalikin LM, Johnson LA, Thompson JS. 1994. Loss of imprinting in human cancer. Cold Spring Harbor Symp. Quant. Biol. 59:357-64
50. Feinberg AP, Vogelstein B. 1983. Hypomethylation of ras oncogenes in primary human cancers. Biochem. Biophys. Res. Commun. 111:47-54
51. Fiskerstrand T, Christensen B, Tysnes OB, Ueland PM, Refsum H. 1994. Development and reversion of methionine dependence in a human glioma cell line: relation to homocysteine remethylation and cobalamin status. Cancer Res. 54:4899-906
52. Frederico LA, Kunkel TA, Shaw BR. 1993. Cytosine deamination in mismatched base pairs. Biochemistry 32:6523-30
53. Fundele RH, Surani MA. 1994. Experimental embryological analysis of genetic imprinting in mouse development. Dev. Genet. 15:515-22
54. Gama-Sosa MA, Slagel VA, Trewyn RW, Oxenhandler R, Kuo KC, et al. 1983. The 5-methylcytosine content of DNA from human tumors. Nucleic Acids Res. 11:6883-94
55. Garcea R, Daino L, Pascale R, Simile MM, Puddu M, et al. 1989. Protooncogene methylation and expression in regenerating liver and preneoplastic liver nodules induced in the rat by diethylnitrosamine: effect of variations of S-adenosylmethionine: S-adenosylhomocysteine ratio. Carcinogenesis 10:1183-92
56. Gardiner-Garden M, Frommer M. 1987. CpG islands in vertebrate genomes. J. Mol. Biol. 196:261-82
57. Ghazi H, Magewu AN, Gonzales F, Jones PA. 1990. Changes in the allelic methylation patterns of c-H-ras-1, insulin and retinoblastoma genes in human development. Dev. Suppl. 1990:115-23
58. Ghoshal AK, Farber E. 1984. The induction of liver cancer by dietary iciency of choline and methionine without added carcinogens. Carcinogenesis 5:1367-70
59. Giovannucci E, Stampfer MJ, Colditz GA, Rimm EB, Trichopoulos D, et al. 1993. Folate, methionine, and alcohol intake and risk of colorectal adenoma. J. Natl. Cancer Inst. 85:875-84
60. Gold JD, Pedersen RA. 1994. Mechanisms of genomic imprinting in mammals. Curr. Top. Dev. Biol. 29:227-80
61. Gonzalez-Zuleta M, Bender CM, Yang AS, Nguyen T, Beart RW, et al. 1995. 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. 55:4531-35
62. Greenblatt MS, Bennett WP, Hollstein M, Harris CC. 1994. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 54:4855-78
63. Greger V, Debus N, Lohmann D, Hopping W, Passarge E, Horsthernke B. 1994. Frequency and parental origin of hypermethylated RB1 alleles in retinoblastoma. Hum. Genet. 94:491-96
64. Greger V, Passarge E, Hopping W, Messmer E, Horsthernke B. 1989. Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum. Genet. 83:155-58
65. Hanada M, Delia D, Aiello A, Stadtmauer E, Reed JC. 1993. bcl-2 gene hypomethylation and high-level expression in B-cell chronic lymphocytic leukemia. Blood 82:1820-28
66. Harris CC, Hollstein M. 1993. Clinical implications of the p53 tumor-suppressor gene. N. Engl. J. Med. 329:1318-27
67. Heby O. 1995. DNA methylation and polyamines in embryonic development and cancer. Int. J. Dev. Biol. 39:737-57
68. Herman JG, Jen J, Merlo A, Baylin SB. 1996. Hypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B1. Cancer Res. 56:722-27
69. Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, et al. 1994. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc. Natl. Acad. Sci. USA 91:9700-4
70. Herman JG, Merlo A, Mao L, Lapidus RG, Issa J-P, et al. 1995. Inactivation of the CDKN2/P16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res. 55:4525-30
71. Hibi K, Nakamura H, Hirai A, Fujikake Y, Kasai Y, et al. 1996. Loss of H19 imprinting in esophageal cancer. Cancer Res. 56:480-82
72. Ho L, Bohr VA, Hanawalt PC. 1989. Demethylation enhances removal of pyrimidine dimers from the overall genome and from specific DNA sequences in Chinese hamster ovary cells. Mol. Cell. Biol. 9:1594-603
73. Hoffman RM. 1984. Altered methionine metabolism, DNA methylation and oncogene expression in carcinogenesis. A review and synthesis. Biochim. Biophys. Acta 738:49-87
74. Hoffman RM. 1985. Altered methionine metabolism and transmethylation in cancer. Anticancer Res. 5:1-30
75. Hoffman RM. 1989. Altered methionine metabolism and unbalanced transmethylation: a possible basis for the dynamic phenotype of cancer. In Absorption and Utiliztion of Amino Acids, ed. M Friedman, 3:1-7. Boca Raton, FL: CRC
76. Hoffman RM, Erbe RW. 1976. High in vivo rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine. Proc. Natl. Acad. Sci. USA 73:1523-27
77. Hollstein M, Rice K, Greenblatt MS, Soussi T, Fuchs R, et al. 1994. Database of p53 gene somatic mutations in human tumors and cell lines. Nucleic Acids Res. 22:3551-55
78. Hsieh CL. 1994. Dependence of transcriptional repression on CpG methylation density. Mol. Cell. Biol. 14:5487-94
79. Issa JP, Vertino PM, Wu J, Sazawal S, Celano P, et al. 1993. Increased cytosine DNA-methyltransferase activity during colon cancer progression. J. Natl. Cancer Inst. 85:1235-40
80. Jones PA. 1985. Altering gene expression with 5-azacytidine. Cell 40:485-86
81. Jones PA, Rideout WM, Shen JC, Spruck CH, Tsai YC. 1992. Methylation, mutation and cancer. BioEssays 14:33-36
82. Jones PA, Taylor SM. 1980. Cellular differentiation, cytidine analogs and DNA methylation. Cell 20:85-93
83. Jones PA, Wolkowicz MJ, Rideout WM, Gonzales FA, Marziasz CM, et al. 1990. De novo methylation of the MyoD1 CpG island during the establishment of immortal cell lines. Proc. Natl. Acad. Sci. USA 87:6117-21
84. Jost JP, Jost YC. 1994. Transient DNA demethylation in differentiating mouse myoblasts correlates with higher activity of 5-methyldeoxycytidine excision repair. J. Biol. Chem. 269:10040-43
85. 84a. Jost JP, Saluz HP, eds. 1993. DNA Methylation: Molecular Biology and Biological Significance. Basel: Birkhauser Verlag
86. Judde JG, Ellis M, Frost P. 1989. Biochemical analysis of the role of transmethylation in the methionine dependence of tumor cells. Cancer Res. 49:4859-65
87. Kafri T, Gao X, Razin A. 1993. Mechanistic aspects of genome-wide demethylation in the preimplantation mouse embryo. Proc. Natl. Acad. Sci. USA 90: 10558-62
88. Kaneko Y, Shibuya M, Nakayama T, Hayashida N, Toda G, et al. 1985. Hypomethylation of c-myc and epidermal growth factor receptor genes in human hepatocellular carcinoma and fetal liver. Jpn. J. Cancer Res. 76:1136-40
89. Kautiainen TL, Jones PA. 1986. DNA methyltransferase levels in tumorigenic and nontumorigenic cells in culture. J. Biol. Chem. 261:1594-98
90. Kelleher JE, Daniel AS, Murray NE. 1991. Mutations that confer de novo activity upon a maintenance methyltransferase. J. Mol. Biol. 221:431-40
91. Klimasauskas S, Kumar S, Roberts RJ, Cheng X. 1994. HhaI methyltransferase flips its target base out of the DNA helix. Cell 76:357-69
92. Klimasauskas S, Roberts RJ. 1995. M.HhaI binds tightly to substrates containing mismatches at the target base. Nucleic Acids Res. 23:1388-95
93. Knudson A Jr. 1971. Mutation and cancer: statistical study of retinoblastoma. Proc. Natl. Acad. Sci. USA 68:820-23
94. Knudson A Jr, Hethcote HW, Brown BW. 1975. Mutation and childhood cancer: a probabilistic model for the incidence of retinoblastoma. Proc. Natl. Acad. Sci. USA 72:5116-20
95. Knudson A Jr, Strong LC. 1972. Mutation and cancer: a model for Wilms' tumor of the kidney. J. Natl. Cancer Inst. 48:313-24
96. Kondo M, Suzuki H, Ueda R, Osada H, Takagi K, et al. 1995. Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. Oncogene 10:1193-98
97. Kumar S, Cheng X, Klimasauskas S, Mi S, Posfai J, et al. 1994. The DNA (cytosine-5) methyltransferases. Nucleic Acids Res. 22:1-10
98. Laayoun A, Smith SS. 1995. Methylation of slipped duplexes, snapbacks and cruciforms by human DNA (cytosine-5) methyltransferase. Nucleic Acids Res. 23:1584-89
99. Laird PW, Jackson-Grusby L, Fazeli A, Dickinson SL, Jung WE, et al. 1995. Suppression of intestinal neoplasia by DNA hypomethylation. Cell 81:197-205
100. Laird PW, Jaenisch R. 1994. DNA methylation and cancer. Hum. Mol. Genet. 3:1487-95
101. Lapeyre JN, Becker FF. 1979. 5-Methylcytosine content of nuclear DNA during chemical hepatocarcinogenesis and in carcinomas which result. Biochem. Biophys. Res. Commun. 87:698-705
102. Lapeyre JN, Walker MS, Becker FF. 1981. DNA methylation and methylase levels in normal and malignant mouse hepatic tissue. Carcinogenesis 2:873-78
103. Lauster R, Trautner TA, Noyer-Weidner M. 1989. Cytosine-specific type II DNA methyltransferases. A conserved enzyme core with variable target-recognizing domains. J. Mol. Biol. 206:305-12
104. Leach RJ, Magewu AN, Buckley JD, Benedict WF, Rother C, et al. 1990. Preferential retention of paternal alleles in human retinoblastoma: evidence for genomic imprinting. Cell Growth Differ. 1:401-6
105. Lei H, Oh S, Okano M, Jütterman R, Goss KA, et al. 1996. De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development. In press
106. Leonhardt H, Bestor TH. 1993. Structure, function and regulation of mammalian DNA methyltransferase. See Ref. 84a, pp. 109-19
107. Levine AJ, Wu MC, Chang A, Silver A, Attiyeh EF, et al. 1995. The spectrum of mutations at the p53 locus. Evidence for tissue-specific mutagenesis, selection of mutant alleles, and a "gain of function" phenotype. Ann. NY Acad. Sci. 768:111-28
108. Li E, Beard C, Jaenisch R. 1993. Role for DNA methylation in genomic imprinting. Nature 366:362-65
109. Li E, Bestor TH, Jaenisch R. 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915-26
110. Liteplo RG. 1990. Reversion to a homocysteine-responsive phenotype in a human melanoma cell line is associated with diminished growth potential and increased methionine biosynthesis. Exp. Cell Res. 186:340-45
111. Little M, Wainwright B. 1995. Methylation and p16: suppressing the suppressor. Nat. Med. 1:633-34
112. Lombardi B, Smith ML. 1994. Tumorigenesis, protooncogene activation, and other gene abnormalities in methyl iciency. J. Nutr. Biochem. 5:2-9
113. MacLeod AR, Szyf M. 1995. Expression of antisense to DNA methyltransferase mRNA induces DNA demethylation and inhibits tumorigenesis. J. Biol. Chem. 270:8037-43
114. Macleod D, Charlton J, Mullins J, Bird AP. 1994. Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev. 8:2282-92
115. 113a. Magewu AN, Jones PA. 1994. Ubiquitous and tenacious methylation of the CpG site in codon 248 of the p53 gene may explain its frequent appearance as a mutational hot spot in human cancer. Mol. Cell Biol. 14:4225-32
116. Malkin D. 1994. Germline p53 mutations and heritable cancer. Annu. Rev. Genet. 28:443-65
117. Mannens M, Hoovers JM, Redeker E, Verjaal M, Feinberg AP, et al. 1994. Parental imprinting of human chromosome region 11p15.3-pter involved in the Beckwith-Wiedemann syndrome and various human neoplasia. Eur. J. Hum. Genet. 2:3-23
118. Mannens M, Slater RM, Heyting C, Bliek J, de Kraker J, et al. 1988. Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 11 in Wilms' tumours. Hum. Genet. 81:41-48
119. Mason JB. 1994. Folate and colonic carcinogenesis: searching for a mechanistic understanding. J. Nutr. Biochem. 5:170-75
120. Menegazzi M, Scarpa A, Libonati M. 1988. Analysis of the methylation pattern of c-Ha-ras oncogene in human prostatic cancer. Ital. J. Biochem. 37:104-10
121. Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, et al 1995. 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat. Med. 1:686-92
122. Mikol YB, Hoover KL, Creasia D, Poirier LA. 1983. Hepatocarcinogenesis in rats fed methyl-deficient, amino acid-defined diets. Carcinogenesis 14:1619-29
123. Mol CD, Arvai AS, Slupphaug G, Kavli B, Alseth I, et al 1995. Crystal structure and mutational analysis of human uracil-DNA glycosylase: structural basis for specificity and catalysis. Cell 80:869-78
124. Moulton T, Crenshaw T, Hao Y, Moosikasuwan J, Lin N, et al. 1994. Epigenetic lesions at the H19 locus in Wilms' tumour patients. Nat. Genet. 7:440-47
125. Muiznieks I, Doerfler W. 1994. The impact of 5′-CG-3′ methylation on the activity of different eukaryotic promoters: a comparative study. FEBS Lett. 344:251-54
126. 123a. Mummaneni P, Bishop PL, Turker MS. 1993. A cis-acting element accounts for a conserved methylation pattern upstream of the mouse adenine phosphoribosyl-transferase gene. J. Biol. Chem. 268:552-58
127. Nambu S, Inoue K, Saski H. 1987. Site-specific hypomethylation of the c-myc oncogene in human hepatocellular carcinoma. Jpn. J. Cancer Res. 78:695-704
128. Neddermann P, Jiricny J. 1994. Efficient removal of uracil from G.U mispairs by the mismatch-specific thymine DNA glycosylase from HeLa cells. Proc. Natl. Acad. Sci. USA 91:1642-46
129. Ogawa O, Eccles MR, Szeto J, McNoe LA, Yun K, et al. 1993. Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour. Nature 362:749-51
130. Ohtani-Fujita N, Fujita T, Aoike A, Osifchin NE, Robbins PD, Sakai T. 1993. CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene. Oncogene 8:1063-67
131. Paroush Z, Keshet I, Yisraeli J, Cedar H. 1990. Dynamics of demethylation and activation of the alpha-actin gene in myoblasts. Cell 63:1229-37
132. Perry ME, Rolfe M, McIntyre P, Commane M, Stark GR. 1992. Induction of gene amplification by 5-aza-2′-deoxycytidine. Mutat. Res. 276:189-97
133. Poirier LA. 1994. Methyl group deficiency in hepatocarcinogenesis. Drug Metab. Rev. 26:185-99
134. Posfai J, Bhagwat AS, Posfai G, Roberts RJ. 1989. Predictive motifs derived from cytosine methyltransferases. Nucleic Acids Res. 17:2421-35
135. Rainier S, Feinberg AP. 1994. Genomic imprinting, DNA methylation, and cancer. J. Natl. Cancer Inst. 86:753-59. Erratum 1994. J. Natl. Cancer Inst. 86(13):1028
136. Rainier S, Johnson LA, Dobry CJ, Ping AJ, Grundy PE, Feinberg AP. 1993. Relaxation of imprinted genes in human cancer. Nature 362:747-49
137. Rao PM, Antony A, Rajalakshmi S, Sarma DS. 1989. Studies on hypomethylation of liver DNA during early stages of chemical carcinogenesis in rat liver. Carcinogenesis 10:933-37
138. Ray JS, Harbison ML, McClain RM, Goodman JI. 1994. Alterations in the methylation status and expression of the raf oncogene in phenobarbital-induced and spontaneous B6C3F1 mouse liver tumors. Mol. Carcinog. 9:155-66
139. Razin A, Cedar H. 1994. DNA methylation and genomic imprinting. Cell 77:473-76
140. Razin A, Kafri T. 1994. DNA methylation from embryo to adult. Prog. Nucleic Acid Res. Mol. Biol. 48:53-81
141. Reinisch KM, Chen L, Verdine GL, Lipscomb WN. 1995. The crystal structure of HaeIII methyltransferase convalently complexed to DNA: an extrahelical cytosine and rearranged base pairing. Cell 82:143-53
142. Rideout WM, Coetzee GA, Olumi AF, Spruck CH, Jones PA. 1991. 5-Methylcytosine as an endogenous mutagen in the p53 tumor suppressor gene. Princess Takamatsu Symp. 22:207-19
143. Rideout WM, Eversole-Cire P, Spruck CH, Hustad CM, Coetzee GA, et al. 1994. Progressive increases in the methylation status and heterochromatinization of the myoD CpG island during oncogenic transformation. Mol. Cell. Biol. 14:6143-52
144. Roberts RJ. 1995. On base flipping. Cell 82:9-12
145. Sakai T, Toguchida J, Ohtani N, Yandell DW, Rapaport JM, Dryja TP. 1991. Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. Am. J. Hum. Genet. 48:880-88
146. Santoro R, D'Erme M, Mastrantonio S, Reale A, Marenzi S, et al. 1995. Binding of histone H1e-c variants to CpG-rich DNA correlates with the inhibitory effect on enzymic DNA methylation. Biochem. J. 305:739-44
147. Santoro R, D'Erme M, Reale A, Strom R, Caiafa P. 1993. Effect of H1 histone isoforms on the methylation of single-or double-stranded DNA. Biochem. Biophys. Res. Commun. 190:86-91
148. Sapienza C. 1991. Genome imprinting and carcinogenesis. Biochim. Biophys. Acta 1072:51-61
149. Sapienza C. 1992. Genome imprinting and cancer genetics. Semin. Cancer. Biol. 3:151-58
150. Savva R, McAuley-Hecht K, Brown T, Pearl L. 1995. The structural basis of specific base-excision repair by uracil-DNA glycosylase. Nature 373:487-93
151. Schluckebier G, O'Gara M, Saenger W, Cheng X. 1995. Universal catalytic domain structure of AdoMet-dependent methyltransferases. J. Mol. Biol. 247:16-20
152. Schmutte C, Yang AS, Beart RW, Jones PA. 1995. Base excision repair of U:G mismatches at a mutational hotspot in the p53 gene is more efficient than base excision repair of T:G mismatches in extracts of human colon tumors. Cancer Res. 55:3742-46
153. Schmutte C, Yang AS, Nguyen TT, Beart RW, Jones PA. 1996. Mechanisms for the involvement of DNA methylation in colon carcinogenesis. Cancer Res. 56:2375-81
154. Schroeder WT, Chao L-Y, Dao DD, Strong LC, Pathak S, et al. 1987. Nonrandom loss of maternal chromosome 11 alleles in Wilms tumors. Am. J. Hum. Genet. 40:413-20
155. Scrable H, Cavenee W, Ghavimi F, Lovell M, Morgan K, Sapienza C. 1989. A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting. Proc. Natl. Acad. Sci. USA 86:7480-84
156. Sharrard RM, Royds JA, Rogers S, Shorthouse AJ. 1992. Patterns of methylation of the c-myc gene in human colorectal cancer progression. Br. J. Cancer 65:667-72
157. Shen JC, Rideout WM, Jones PA. 1992. High frequency mutagenesis by a DNA methyltransferase. Cell 71:1073-80
158. Shen JC, Rideout WM, Jones PA. 1994. The rate of hydrolytic deamination of 5-methylcytosine in double-stranded DNA. Nucleic Acids Res. 22:972-76
159. Shen JC, Zingg JM, Yang AS, Schmutte C, Jones PA. 1995. A mutant HpaII methyltransferase functions as a mutator enzyme. Nucleic Acids Res. 23:4275-82
160. Simile MM, Pascale R, De Miglio MR, Nufris A, Daino L, et al. 1994. Correlation between S-adenosyl-L-methionine content and production of c-myc, c-Ha-ras, and c-Ki-ras mRNA transcripts in the early stages of rat liver carcinogenesis. Cancer Lett. 79:9-16
161. Smith SS. 1994. Biological implications of the mechanism of action of human DNA (cytosine-5) methyltransferase. Prog. Nucleic Acid Res. Mol. Biol. 49:65-111
162. Smith SS, Kan JL, Baker DJ, Kaplan BE, Dembek P. 1991. Recognition of unusual DNA structures by human DNA (cytosine-5) methyltransferase. J. Mol. Biol. 217:39-51
163. Smith SS, Laayoun A, Lingeman RG, Baker DJ, Riley J. 1994. Hypermethylation of telomere-like foldbacks at codon 12 of the human c-Ha-ras gene and the trinucleotide repeat of the FMR-1 gene of fragile X. J. Mol. Biol. 243:143-51
164. Spruck CH, Rideout WM, Jones PA. 1993. DNA methylation and cancer. See Ref. 84a, pp. 487-509
165. Steenman MJ, Rainier S, Dobry CJ, Grundy P, Horon IL, Feinberg AP. 1994. Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour. Nat. Genet. 7:433-39
166. Steinberg RA, German KB. 1992. Linked spontaneous CG-TA mutations at CpG sites in the gene for protein kinase regulatory subunit. Mol. Cell. Biol. 12:767-72
167. Stephenson J, Akdag R, Ozbek N, Mufti GJ. 1993. Methylation status within exon 3 of the c-myc gene as a prognostic marker in myeloma and leukaemia. Leuk. Res. 17:291-93
168. Stern PH, Hoffman RM. 1984. Elevated overall rates of transtnethylation in cell lines from diverse human tumors. In Vitro 20:663-70
169. Stern PH, Mecham JO, Wallace CD, Hoffman RM. 1983. Reduced free-methionine in methionine-dependent SV40-transformed human fibroblasts synthesizing apparently normal amounts of methionine. J. Cell. Physiol. 117:9-14
170. Stern PH, Wallace CD, Hoffman RM. 1984. Altered methionine metabolism occurs in all members of a set of diverse human tumor cell lines. J. Cell. Physiol. 119:29-34
171. Stoner GD, Shimkin MB, Kniazeff AJ, Weisburger JH, Weisburger EK, Gori GB. 1973. Test for carcinogenicity of food additives and chemotherapeutic agents by the pulmonary response in strain A mice. Cancer Res. 33:3069-85
172. Strom R, Santoro R, D'Erme M, Mastrantonio S, Reale A, et al. 1995. Specific variants of H1 histone regulate CpG methylation in eukaryotic DNA. Gene 157:253-56
173. Szyf M. 1994. DNA methylation properties: consequences for pharmacology. Trends Pharmacol. Sci. 15:233-38
174. Taniguchi T, Sullivan MJ, Ogawa O, Reeve AE. 1995. Epigenetic changes encompassing the IGF2/H19 locus associated with relaxation of IGF2 imprinting and silencing of H19 in Wilms tumor. Proc. Natl. Acad. Sci. USA 92:2159-63
175. Taylor SM, Jones PA. 1979. Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell 17:771-79
176. Thomas GA, Williams ED. 1992. Production of thyroid tumours in mice by demethylating agents. Carcinogenesis 13:1039-42
177. Toguchida J, Ishizaki K, Sasaki MS, Nakamura Y, Ikenaga M, et al. 1989. Preferential mutation of paternally derived RB gene as the initial event in sporadic osteosarcoma. Nature 338:156-58
178. Tomaletti S, Pfeifer GP. 1995. Complete and tissue-independent methylation of CpG sites in the p53 gene: implications for mutations in human cancers. Oncogene 10:1493-99
179. Trasler JM, Hake LE, Johnson PA, Alcivar AA, Millette CF, Hecht NB. 1990. DNA methylation and demethylation events during meiotic prophase in the mouse testis. Mol. Cell. Biol. 10:1828-34
180. Tucker KL, Beard C, Dausman J, Jackson-Grusby L, Laird PW, et al. 1996. Germ-line passage is required for establishment of methylation patterns of imprinted but not of nonimprinted genes. Genes Dev. 10:1008-20
181. Tulchinsky E, Grigorian M, Tkatch T, Georgiev G, Lukanidin E. 1995. Transcriptional regulation of the mts1 gene in human lymphoma cells: the role of DNA-methylation. Biochim. Biophys. Acta 1261:243-48
182. Vachtenheim J, Horakova I, Novotna H. 1994. Hypomethylation of CCGG sites in the 3′ region of H-ras protooncogene is frequent and is associated with H-ras allele loss in nonsmall cell lung cancer. Cancer Res. 54:1145-48
183. Vairapandi M, Duker NJ. 1993. Enzymic removal of 5-methylcytosine from DNA by a human DNA-glycosylase. Nucleic Acids Res. 21:5323-27
184. van Gurp RJ, Oosterhuis JW, Kalscheuer V, Mariman EC, Looijenga LH. 1994. Biallelic expression of the H19 and IGF2 genes in human testicular germ cell tumors. J. Natl. Cancer Inst. 86:1070-75
185. Verdine GL. 1994. The flip side of DNA methylation. Cell 76:197-200
186. Vorce RL, Goodman JI. 1989. Altered methylation of ras oncogenes in benzidine-induced B6C3F1 mouse liver tumors. Toxicol. Appl. Pharmacol. 100:398-410
187. Vorce RL, Goodman JI. 1989. Hypomethylation of ras oncogenes in chemically induced and spontaneous B6C3F1 mouse liver tumors. Mol. Toxicol. 2:99-116
188. Williams JC, Brown KW, Mott MG, Maitland NJ. 1989. Maternal allele loss in Wilms' tumour. Lancet 1:283-84
189. Wilson GG, Murray NE. 1991. Restriction and modification systems. Annu. Rev. Genet. 25:585-627
190. Woodcock DM, Crowther PJ, Diver WP. 1987. The majority of methylated deoxycytidines in human DNA are not in the CpG dinucleotide. Biochem. Biophys. Res. Commun. 145:888-94
191. Wu JC, Santi DV. 1985. On the mechanism and inhibition of DNA cytosine methyltransferases. In Biochemistry and Biology of DNA Methylation. Prog. Clin. Biol. Res. 198:119-29. New York: Liss
192. Wu JC, Santi DV. 1987. Kinetic and catalytic mechanism of HhaI methyltransferase. J. Biol. Chem. 262:4778-86
193. Wu JJ, Issa JP, Herman J, Bassett DE Jr, Nelkin BD, Baylin SB. 1993. Expression of an exogenous eukaryotic DNA methyltransferase gene induces transformation of NIH 3T3 cells. Proc. Natl. Acad. Sci. USA 90:8891-95
194. Wyszynski M, Gabbara S, Bhagwat AS. 1994. Cytosine deaminations catalyzed by DNA cytosine methyltransferases are unlikely to be the major cause of mutational hot spots at sites of cytosine methylation in Escherichia coli. Proc. Natl. Acad. Sci. USA 91:1574-78
195. Yang AS, Gonzalgo ML, Zingg J-M, Millar RP, Buckley JD, Jones PA. 1996. The rate of CpG mutation in Alu repetitive elements within the p53 tumor suppressor gene in the primate germline. J. Mol. Biol. 258:240-50
196. Yang AS, Shen JC, Zingg J-M, Mi S, Jones PA. 1995. HhaI and HpaII DNA methyltransferases bind DNA mismatches, methylate uracil and block DNA repair. Nucleic Acids Res. 23:1380-87
197. Yebra MJ, Bhagwat AS. 1995. A cytosine methyltransferase converts 5-methylcytosine in DNA to thymine. Biochemistry 34:14752-57
198. Yeivin A, Razin A. 1993. Gene methylation patterns and expression. See Ref. 84a, pp. 523-68
199. Zhang Y, Shields T, Crenshaw T, Hao Y, Moulton T, Tycko B. 1993. Imprinting of human H19: allele-specific CpG methylation, loss of the active allele in Wilms tumor, and potential for somatic allele switching. Am. J. Hum. Genet. 53:113-24
200. Zhu XP, Dunn JM, Phillips RA, Goddard AD, Paton KE, et al. 1989. Preferential germline mutation of the paternal allele in retinoblastoma. Nature 340:312-13
201. Zion M, Ben-Yehuda D, Avraham A, Cohen O, Wetzler M, et al. 1994. Progressive de novo DNA methylation at the bcr-abl locus in the course of