The DNA methylation machinery as a target for anticancer therapy

Pharmacology and Therapeutics

Volumn 70, Issue 1, 1996, Pages 1-37

  Szyf, Moshe ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

5 deoxyazacytidine; anticancer agents; de novo methylation; demethylation; DNA methylation; epigenetic modification

Indexed keywords

ANTINEOPLASTIC AGENT; AZACITIDINE; DNA METHYLTRANSFERASE; ENZYME INHIBITOR;

CANCER; CANCER GENETICS; DNA METHYLATION; GENE CONTROL; GENE EXPRESSION; GENE REPLICATION; GENE THERAPY; GENOME; HUMAN; MUTATION; ONCOGENE; PRIORITY JOURNAL; REVIEW; TUMOR SUPPRESSOR GENE;

EID: 0029946249     PISSN: 01637258     EISSN: None     Source Type: Journal    
DOI: 10.1016/0163-7258(96)00002-2     Document Type: Review

References (331)

1. Aarbakke, J., Miura, G. A., Prytz, P. S., Bessesen, A., Slordal, L., Gordon, R. K. and Chiang, P. K. (1986) Induction of HL-60 cell differentiation by 3-deaza-(±)-aristeromycin, an inhibitor of S-adenosylhomocysteine hydrolase. Cancer Res. 46: 5469-5472.
2. Amacher, D. E. and Turner, G. N. (1987) The mutagenicity of 5-azacytidine and other inhibitors of replicative DNA synthesis in the L5178Y mouse lymphoma cell. Mutat. Res. 176: 123-131.
3. Angel, P. and Karin, M. (1991) The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim. Biophys. Acta 1072: 129-157.
4. Antequera, F., Boyes, J. and Bird, A. (1990) High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines. Cell 62: 503-514.
5. Ariel, M., Robinson, E., Mccarrey, J. R. and Cedar, H. (1995) Gamete-specific methylation correlates with imprinting of the murine Xist gene. Nat. Genet. 9: 312-315.
6. Arnold, T. E., Farrance, I. K., Morris, J. and Ivarie, R. (1991) Prolactin-deficient GH3B3 cells are defective in the utilization of the endogenous prolactin promoter yet are fully competent to initiate transcription from a transfected prolactin promoter. DNA Cell Biol. 10: 105-112.
7. Attadia, V. (1993) Effects of 5-aza-2′-deoxycytidine on differentiation and oncogene expression in the human monoblastic leukemia cell line U-937. Leukemia 7 (Suppl. 1): 9-16.
8. Bakker, A. and Smith, D. W. (1989) Methylation of GATC sites is required for precise timing between rounds of DNA replication in Escherichia coli. J. Bacteriol. 171: 5738-5742.
9. Barletta, J. and Greer, S. B. (1992) Methylation of HSV-1 DNA as a mechanism of viral inhibition: studies of an analogue of methyldeoxycytidine trifluoromethyldeoxycytidine (F3mdCyd). Antiviral Res. 18: 1-25.
10. Bartolomei, M. S., Webber, A. L., Brunkow, M. E. and Tilghman, S. M. (1993) Epigenetic mechanisms underlying the imprinting of the mouse H19 gene. Genes Dev. 7: 1663-1673.
11. Baylin, S. B., Hoppener, J. W., de Bustros, A., Steenbergh, P. H., Lips, C. J. and Nelkin, B. D. (1986) DNA methylation patterns of the calcitonin gene in human lung cancers and lymphomas. Cancer Res. 46: 2917-2922.
12. Baylin, S. B., Makos, M., Wu, J. J., Yen, R. W., de Bustros, A., Vertino, P. and Nelkin, B. D. (1991) Abnormal patterns of DNA methylation in human neoplasia: potential consequences for tumor progression. Cancer Cells 3: 383-390.
13. Becker, P. B., Ruppert, S. and Schutz, G. (1987) Genomic footprinting reveals cell type-specific DNA binding of ubiquitous factors. Cell 51: 435-443.
14. Benoit, G. and Trasler, J. M. (1994) Developmental expression of DNA methyltransferase messenger ribonucleic acid, protein, and enzyme activity in the mouse testis. Biol. Reprod. 50: 1312-1319.
15. Benvenisty, N., Mencher, D, Meyuhas, O., Razin, A. and Reshef, L. (1985) Sequential changes in DNA methylation patterns of the rat phosphoenolpyruvate carboxykinase gene during development. Proc. Natl. Acad. Sci. USA. 82: 267-271.
16. Bestor, T. H. and Ingram, V. M. (1983) Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA. Proc. Natl. Acad. Sci. USA 80: 5559-5563.
17. Bestor, T. H., Hellewell, S. B. and Ingram, V. M. (1984) Differentiation of two mouse cell lines is associated with hypomethylation of their genomes. Mol. Cell. Biol. 4: 1800-1806.
18. Bestor, T. H., Laudano, A., Mattaliano, R. and 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: 971-983.
19. Biggin, M. D., Bickel, S., Benson, M., Pirrotta, V. and Tjian, R. (1988) Zeste encodes a sequence-specific transcription factor that activates the Ultrabithorax promoter in vitro. Cell 53: 713-722.
20. Binetruy, B., Smeal, T. and Karin, M. (1991) Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domain. Nature 351: 122-127.
21. Bird, A., Taggart, M., Frommer, M., Miller, O. J. and Macleod, D. (1985) A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell 40: 91-99.
22. Bouchard, J., Walker, M. C., Leclerc, J. M., Lapointe, N., Beaulieu, R. and Thibodeau, L. (1990) 5-Azacytidine and 5-azadeoxy-cytidine inhibit human immunodeficiency virus type 1 replication in vitro. Antimicrob. Agents Chemother. 34: 206-209.
23. Boye, E. and Lobner-Olesen, A. (1990) The role of dam methyltransferase in the control of DNA replication in E. coli. Cell 62: 981-989.
24. Boyes, J. and Bird, A. (1991) DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell 64: 1123-1134.
25. Boyes, J. and Bird, A. (1992) Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl-CpG binding protein. EMBO J. 11: 327-333.
26. Brandeis, M., Ariel, M. and Cedar, H. (1993a) Dynamics of DNA methylation during development. Bioessays 15: 709-713.
27. Brandeis, M., Kafri, T., Ariel, M., Chaillet, J. R., McCarrey, J., Razin, A. and Cedar, H. (1993b) The ontogeny of allele-specific methylation associated with imprinted genes in the mouse. EMBO J. 12: 3669-3677.
28. Brandeis, M., Frank, D., Keshet, I., Siegfried, Z., Mendelsohn, M., Nemes, A., Temper, V., Razin, A. and Cedar, H. (1994) Sp1 elements protect a CpG island from de novo methylation. Nature 371: 435-438.
29. Brown, C. J., Ballabio, A., Rupert, J. L., Lafreniere, R. G., Grompe, M., Tonlorenzi, R. and Willard, H. F. (1991) A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349: 38-44.
30. Bruhat, A. and Jost, J. P. (1995) In vivo estradiol-dependent dephosphorylation of the repressor MDBP-2-H1correlates with the loss of in vitro preferential binding to methylated DNA. Proc. Natl. Acad. Sci. USA 92: 3678-3682.
31. Bryans, M., Kass, S., Seivwright, C. and Adams, R. L. (1992) Vector methylation inhibits transcription from the SV40 early promoter. FEBS Lett. 309: 97-102.
32. Busslinger, M., Hurst, J. and Flavell, R. A. (1983) DNA methylation and the regulation of globin gene expression. Cell 34: 197-206.
33. Caiafa, P., Reale, A., D'Erme, M., Allegra, P., Santoro, R. and Strom, R. (1991) Histones and DNA methylation in mammalian chromatin. II. Presence of noninhibitory tightly bound histones. Biochim. Biophys. Acta 1129: 43-48.
34. Call, K. M., Jensen, J. C., Liber, H. L. and Thilly, W. G. (1986) Studies of mutagenicity and clastogenicity of 5-azacytidine in human lymphoblasts and Salmonella typhimurium. Mutat. Res. 160: 249-257.
35. Campbell, J. L. and Kleckner, N. (1990) E. coli oriC and the dnaA gene promoter are sequestered from dam methyltransferase following the passage of the chromosomal replication fork. Cell 62: 967-979.
36. Carlson, L. L., Page, A. W. and Bestor, T. H. (1992) Properties and localization of DNA methyltransferase in preimplantation mouse embryos: implications for genomic imprinting. Genes Dev. 6: 2536-2541.
37. Carpinelli, P., Granata, F., Augusti-Tocco, G., Rossi, M. and Bartolucci, S. (1993) Antiproliferative effects and DNA hypomethylation by 5-aza-2′-deoxycytidine in human neuroblastoma cell lines. Anti-Cancer Drugs 4: 629-635.
38. Carr, B. I., Reilly, J. G., Smith, S. S., Winberg, C. and Riggs, A. (1984) The tumorigenicity of 5-azacytidine in the male Fischer rat. Carcinogenesis 5: 1583-1590.
39. Carr, B. I., Rahbar, S., Asmeron, Y., Riggs, A. and Winberg, C. D. (1988) Carcinogenicity and haemoglobin synthesis induction by cytidine analogues. Br. J. Cancer. 57: 395-402.
40. Cavaliere, A., Bufalari, A. and Vitali, R. (1987) 5-Azacytidine carcinogenesis in BALB/c mice. Cancer Lett. 37: 51-58.
41. Cawthon, R. M., Weiss, R., Xu, G. F., Viskochill, D., Culver, M., Stevens, J., Robertson, M., Dunn, D., Gesteland, R., O'Connell, P. and White, R. (1990) A major segment of the Neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell 61: 193-201.
42. Cedar, H. (1988) DNA methylation and gene activity. Cell 53: 3-4.
43. Challita, P. M. and Kohn, D. B. (1994) Lack of expression from a retroviral vector after transduction of murine hematopoietic stem cells is associated with methylation in vivo. Proc. Natl. Acad. Sci. USA 91: 2567-2571.
44. Challita, P. M., Skelton, D., el-Khoueiry, A., Yu, X. J., Weinberg, K. and Kohn, D. B. (1995) Multiple modifications in cis elements of the long terminal repeat of retroviral vectors lead to increased expression and decreased DNA methylation in embryonic carcinoma cells. J. Virol. 69: 748-755.
45. Chapman, V., Forrester, L., Sanford, J., Hastie, N. and Rossant, J. (1984) Cell lineage-specific undermethylation of mouse repetitive DNA. Nature 307: 284-286.
46. Chen, J. and Jones, P. A. (1990) Potentiation of MyoD1 activity by 5-aza-2′-deoxycytidine. Cell Growth Differ. 1: 383-392.
47. Chen, L., MacMillan, A. M., Chang, W., Ezaz-Nikpay, K., Lane, W. S. and Verdine, G. L. (1991) Direct identification of the active-site nucleophile in a DNA (cytosine-5)-methyltransferase. Biochemistry 30: 11018-11025.
48. Cheng, X., Kumar, S., Posfai, J., Pflugrath, J. W. and Roberts, R. J. (1993) Crystal structure of the HhaI DNA methyltransferase complexed with S-adenosyl-L-methionine. Cell 74: 299-307.
49. Chesnokov, I. N. and Schmid, C. W. (1995) Specific Alu binding protein from human sperm chromatin prevents DNA methylation. J. Biol. Chem. 270: 18539-18542.
50. Chiang, P. K. (1984) S-Adenosylhomocysteine hydrolase as a pharmacological target for the inhibition of transmethylation. Adv. Exp. Med. Biol. 165 (Pt. B): 199-203.
51. Chiang, P. K., Burbelo, P. D., Brugh, S. A., Gordon, R. K., Fukuda, K. and Yamada, Y. (1992) Activation of collagen IV gene expression in F9 teratocarcinoma cells by 3-deazaadenosine analogs. Indirect inhibitors of methylation. J. Biol. Chem. 267: 4988-4991.
52. Christman, J. K., Mendelsohn, N., Herzog, D. and Schneiderman, N. (1983) Effect of 5-azacytidine on differentiation and DNA methylation in human promyelocytic leukemia cells (HL-60). Cancer Res. 43: 763-769,
53. Christman, J. K., Sheikhnejad, G., Dizik, M., Abileah, S. and Wainfan, E. (1993) Reversibility of changes in nucleic acid methylation and gene expression induced in rat liver by severe dietary methyl deficiency. Carcinogenesis 14: 551-557.
54. Church, G. M. and Gilbert, W. (1984) Genomic sequencing. Proc. Natl. Acad. Sci. USA 81: 1991-1995.
55. Clark, S. J., Harrison, J., Paul, C. L. and Frommer, M. (1994) High sensitivity mapping of methylated cytosines. Nucl. Acids Res. 22: 2990-2997.
56. Clark, S., Harrison, J. and Frommer, M. (1995) CpNpG methylation in mammalian cells. Nat. Genet. 10: 20-27.
57. Comb, M. and Goodman, H. M. (1990) CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2. Nucl. Acids Res. 18: 3975-3982.
58. Constantinides, P. G., Jones, P. A. and Gevers, W. (1977) Functional striated muscle cells from nonmyoblast precursors following 5-azacytidine treatment. Nature 267: 364-366.
59. Cortvrindt, R., Bernheim, J., Buyssens, N. and Roobol, K. (1987) 5-Azacytidine and 5-aza-2′-deoxycytidine behave as different anti-neoplastic agents in B16 melanoma. Br. J. Cancer 56: 261-265.
60. Counts, J. L. and Goodman, J. I. (1994) Hypomethylation of DNA: an epigenetic mechanism involved in tumor promotion. Mol. Carcinog. 11: 185-188.
61. Coverley, D. and Laskey, R. A. (1994) Regulation of eukaryotic DNA replication. Annu. Rev. Biochem. 63: 745-776.
62. Covey, J. M., D'Incalci, M., Tilchen, E. J., Zaharko, D. S. and Kohn, K. W. (1986) Differences in DNA damage produced by incorporation of 5-aza-2′-deoxycytidine or 5,6-dihydro-5-azacytidine into DNA of mammalian cells. Cancer Res. 46: 5511-5517.
63. Creusot, F., Acs, G. and Christman, J. K. (1982) Inhibition of DNA methyltransferase and induction of Friend erythroleukemia cell differentiation by 5-azacytidine and 5-aza-2′-deoxycytidine. J. Biol. Chem. 257: 2041-2048.
64. Croston, G. E. and Kadonaga, J. T. (1993) Role of chromatin structure in the regulation of transcription by RNA polymerase II. Curr. Opin. Cell Biol. 5: 417-423.
65. Croteau, S. and Menezo, Y. (1994) Methylation in fertilised and parthenogenetic preimplantation mouse embryos. Zygote 2: 47-52.
66. Davar, G., Kramer, M. F., Garber, D., Roca, A. L., Andersen, J. K., Bebrin, W., Coen, D. M., Kosz-Vnenchak, M., Knipe, D. M. and Breakefield, X. O. (1992) Comparative efficacy of expression of genes delivered to mouse sensory neurons with herpes virus vectors. J. Comp. Neurol. 1: 3-11.
67. Davis, R. L., Weintraub, H. and Lassar, A. B. (1987) Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell 51: 987-1000.
68. de Bustros, A., Nelkin, B. D., Silverman, A., Ehrlich, G., Poiesz, B. and Baylin, S. B. (1988) The short arm of chromosome 11 is a "hot spot" for hypermethylation in human neoplasia. Proc. Natl. Acad. Sci. USA 85: 5693-5697.
69. D'Erme, M., Santoro, R., Allegra, P., Reale, A., Marenzi, S., Strom, R. and Caiafa, P. (1993) Inhibition of CpG methylation in linker DNA by H1 histone. Biochim. Biophys. Acta 1173: 209-216.
70. DeSimone, J., Heller, P., Hall, L. and Zwiers, D. (1982) 5-Azacytidine stimulates fetal hemoglobin synthesis in anemic baboons. Proc. Natl. Acad. Sci. USA 79: 4428-4431.
71. Djalali, M., Adolph, S., Steinbach, P., Winking, H. and Hameister, H. (1990) Fragile sites induced by 5-azacytidine and 5-azadeoxy-cytidine in the murine genome. Hereditas 112: 77-81.
72. Doerfler, W. (1991) Patterns of DNA methylation-evolutionary vestiges of foreign DNA inactivation as a host defense mechanism. A proposal. Biol. Chem. Hoppe Seyler 372: 557-564.
73. Efstratiadis, A. (1994) Parental imprinting of autosomal mammalian genes. Curr. Opin. Genet. Dev. 4: 265-280.
74. Ehrlich, M. and Ehrlich, K. C. (1993) Effect of DNA methylation on the binding of vertebrate and plant proteins to DNA. EXS 64: 145-168.
75. Ehrlich, M., Gama-Sosa, M. A., Huang, L. H., Midgett, R. M., Kuo, K. C., McCune, R. A. and Gehrke, C. (1982) Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells. Nucl. Acids Res. 10: 2709-2721.
76. el-Deiry, W. S., Nelkin, B. D., Celano, P., Yen, R. W., Falco, J. P., Hamilton, S. R. and Baylin, S. B. (1991) High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer. Proc. Natl. Acad. Sci. USA 88: 3470-3474.
77. Elledge, S. J. and Harper, J. W. (1994) Cdk inhibitors: on the threshold of checkpoints and development. Curr. Opin. Cell Biol. 6: 847-852.
78. Enver, T., Zhang, J. W., Papayannopoulou, T. and Stamatoyannopoulos, G. (1988) DNA methylation: a secondary event in globin gene switching? Genes Dev. 2: 698-706.
79. Eversole-Cire, P., Ferguson-Smith, A. C., Sasaki, H., Brown, K. D., Cattanach, B. M., Gonzales, F. A., Surani, M. A. and Jones, P. A. (1993) Activation of an imprinted Igf 2 gene in mouse somatic cell cultures. Mol. Cell. Biol. 13: 4928-4938.
80. Feinberg, A. P. and Vogelstein, B. (1983) Hypomethylation distinguishes genes of some human cancers from their normal counter-parts. Nature 301: 89-92.
81. Feinberg, A. P., Gehrke, C. W., Kuo, K. C. and Ehrlich, M. (1988) Reduced genomic 5-methylcytosine content in human colonic neoplasia. Cancer Res. 48: 1159-1161.
82. Flanagan, J. R., Krieg, A. M., Max, E. E. and Khan, A. S. (1989) Negative control region at the 5′ end of murine leukemia virus long terminal repeats. Mol. Cell. Biol. 9: 739-746.
83. Forejt, J. and Gregorova, S. (1992) Genetic analysis of genomic imprinting: an Imprintor-1 gene controls inactivation of the paternal copy of the mouse Tme locus. Cell 70: 443-450.
84. Foss, H. M., Roberts, C. J., Claeys, K. M. and Selker, E. U. (1993) Abnormal chromosome behavior in Neurospora mutants defective in DNA methylation. Science 262: 1737-1741.
85. Frank, D., Keshet, I., Shani, M., Levine, A., Razin, A. and Cedar, H. (1991) Demethylation of CpG islands in embryonic cells. Nature 351: 239-241.
86. Frommer, M., McDonald, L. E., Millar, D. S., Collis, C. M., Watt, F., Grigg, G. W., Molloy, P. L. and Paul C. L. (1992) A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc. Natl. Acad. Sci. USA 89: 1827-1831.
87. Frost, P., Abbruzzese, J. L., Hunt, B., Lee, D. and Ellis, M. (1990) Synergistic cytotoxicity using 2′-deoxy-5-azacytidine and cisplatin or 4-hydroperoxycyclophosphamide with human tumor cells. Cancer Res. 50: 4572-4577.
88. Gama-Sosa, M. A., Midgett, R. M., Slagel, V. A., Githens, S., Kuo, K. C., Gehrke, C. W. and Ehrlich, M. (1983a) Tissue-specific differences in DNA methylation in various mammals. Biochim. Biophys. Acta 740: 212-219.
89. Gama-Sosa, M. A., Slagel, V. A., Trewyn, R. W., Oxenhandler, R., Kuo, K. C., Gehrke, C. W. and Ehrlich, M. (1983) The 5-methylcytosine content of DNA from human tumors. Nucl. Acids Res. 11: 6883-6894.
90. Gambari, R., del Senno, L., Barbieri, R., Viola, L., Tripodi, M., Raschella, G. and Fantoni, A. (1984) Human leukemia K-562 cells: induction of erythroid differentiation by 5-azacytidine. Cell Diff. 14: 87-97.
91. Gartler, S. M. and Riggs, A. D. (1983) Mammalian X-chromosome inactivation. Annu. Rev. Genet. 17: 155-190.
92. Gasson, J. C., Ryden, T. and Bourgeois, S. (1983) Role of de novo DNA methylation in the glucocorticoid resistance of a T-lymphoid cell line. Nature 302: 621-623.
93. Gautsch, J. W. and Wilson, M. C. (1983) Delayed de novo methylation in teratocarcinoma suggests additional tissue-specific mechanisms for controlling gene expression. Nature 301: 32-37.
94. Gillies, S. D., Morrison, S. L., Oi, V. T. and Tonegawa, S. (1983) A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell 33: 717-728.
95. Gjerset, R. A. and Martin, D. W., Jr. (1982) Presence of a DNA demethylating activity in the nucleus of murine erythroleukemic cells. J. Biol. Chem. 257: 8581-8583.
96. Glickman, J. F. and Reich, N. O. (1994) Baculovirus-mediated high level expression of a mammalian DNA methyltransferase. Biochem. Biophys. Res. Commun. 204: 1003-1008.
97. Goelz, S. E., Vogelstein, B., Hamilton, S. R. and Feinberg, A. P. (1985) Hypomethylation of DNA from benign and malignant human colon neoplasms. Science 228: 187-190.
98. Graessmann, A. and Graessmann, M. (1988) DNA methylation, chromatin structure and regulation of Herpes simplex virus tk gene expression. Gene 74: 135-137.
99. Gruenbaum, Y., Cedar, H. and Razin, A. (1981a) Restriction enzyme digestion of hemimethylated DNA. Nucl. Acids Res. 9: 2509-2515.
100. Gruenbaum, Y., Stein, R., Cedar, H. and Razin, A. (1981b) Methylation of CpG sequences in eukaryotic DNA. FEBS Lett. 124: 67-71.
101. Gruenbaum, Y., Cedar, H. and Razin, A. (1982) Substrate and sequence specificity of a eukaryotic DNA methylase. Nature 295: 620-622.
102. Guha, S. (1984) Effect of 5-azacytidine on DNA methylation and on the enzymes of de novo pyrimidine biosynthesis in Bacillus subtilis Marburg strain. Eur. J. Biochem. 145: 99-106.
103. Hansen, R. S. and Gartler, S. M. (1990) 5-Azacytidine-induced reactivation of the human X chromosome-linked PGK1 gene is associated with a large region of cytosine demethylation in the 5′ CpG island. Proc. Natl. Acad. Sci. USA 87: 4174-4178.
104. Harbers, K., Schnieke, A., Stuhlmann, H., Jahner, D. and Jaenisch, R. (1981) DNA methylation and gene expression: endogenous retroviral genome becomes infectious after molecular cloning. Proc. Natl. Acad. Sci. USA 78: 7609-7613.
105. Hasse, A. and Schulz, W. A. (1994) Enhancement of reporter gene de novo methylation by DNA fragments from the alpha-fetoprotein control region. J. Biol. Chem. 269: 1821-1826.
106. Hasse, A., Schulz, W. A. and Sies, H. (1992) De novo methylation of transfected CAT gene plasmid constructs in F9 mouse embryonal carcinoma cells. Biochim. Biophys. Acta 1131: 16-22.
107. Hastie, N. D. (1994) The genetics of Wilms' tumor-a case of disrupted development. Annu. Rev. Genet. 28: 523-558.
108. Herman, J. G., Latif, F., Weng, Y., Lerman, M. I., Zbar, B., Liu, S., Samid, D., Duan, D. S., Gnarra, J. R., Linehan, W. M. and Baylin, S. B. (1994) Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc. Natl. Acad. Sci. USA 91: 9700-9704.
109. Hermann, R. and Doerfler, W. (1991) Interference with protein binding at AP2 sites by sequence-specific methylation in the late E2A promoter of adenovirus type 2 DNA. FEBS Lett. 281: 191-195.
110. Hermonat, P. L. and Muzyczka, N. (1984) Use of adeno-associated virus as a mammalian DNA cloning vector: transduction of neomycin resistance into mammalian tissue culture cells. Proc. Natl. Acad. Sci. USA 81: 6466-6470.
111. Herschman, R. H. (1991) Primary response genes induced by growth factors and tumor promoters. Annu. Rev. Biochem. 60: 281-319.
112. Higurashi, M. and Cole, R. D. (1991) The combination of DNA methylation and H1 histone binding inhibits the action of a restriction nuclease on plasmid DNA. J. Biol. Chem. 266: 8619-8625.
113. Hinds, P. W. and Weinberg, R. A. (1994) Tumor suppressor genes. Curr. Opin. Genet. Dev. 4: 135-141.
114. Holliday, R. (1990) DNA methylation and epigenetic inheritance. Philos. Trans. R. Soc. Lond. B Biol. Sci. 326: 329-338.
115. Holliday, R. and Pugh, J. E. (1975) DNA modification mechanisms and gene activity during development. Science 187:226-232.
116. Hotchkiss, R. D. (1948) The quantitative separation of purines, pyrimidines, and nucleosides by paper chromatography. J. Biol. Chem. 175: 315-332.
117. Hsiao, W. L., Gattoni-Celli, S. and Weinstein, I. B. (1985) Effects of 5-azacytidine on the progressive nature of cell transformation. Mol. Cell. Biol. 5: 1800-1803.
118. Hsieh, C.-L. (1994) Dependence of transcriptional repression on CpG methylation density. Mol. Cell. Biol. 14: 5487-5494.
119. Huang, L. H., Wang, R., Gama-Sosa, M. A., Shenoy, S. and Ehrlich, M. (1984) A protein from human placental nuclei binds preferentially to 5-methylcytosine-rich DNA. Nature 308: 293-295.
120. Ingram, V. M. (1956) A specific chemical difference between the globins of normal human and sickle cell anemia haemoglobin. Nature 178: 792-794.
121. Jahner, D. and Jaenisch, R. (1985) Retrovirus-induced de novo methylation of flanking host sequences correlates with gene inactivity. Nature 315: 594-597.
122. Jane, S. M., Gumucio, D. L., Ney, P. A., Cunningham, J. M. and Nienhuis, A. W. (1993) Methylation-enhanced binding of Sp1 to the stage selector element of the human gamma-globin gene promoter may regulate development specificity of expression. Mol. Cell. Biol. 13: 3272-3281.
123. Jehn, U. (1989) New drugs in the treatment of acute and chronic leukaemia: current role of mAMSA. Bone Marrow Transplant. 4 (Suppl. 3): 53-58.
124. Joel, P., Shao, W. and Pratt, K. (1993) A nuclear protein with enhanced binding to methylated Sp1 sites in the AIDS virus promoter. Nucl. Acids Res. 21: 5786-5793.
125. Johnson, C. A., Goddard, J. P. and Adams, R. L. (1995) The effect of histone H1 and DNA methylation on transcription. Biochem. J. 305: 791-798.
126. Jones, P. A. (1985) Altering gene expression with 5-azacytidine. Cell 40: 485-486.
127. Jones, P. A., Wolkowicz, M. J., Harrington, M. A. and Gonzales, F. (1990a) Methylation and expression of the Myo D1 determination gene. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 326: 277-284.
128. Jones, P. A., Wolkowicz, M. J., Rideout, W. M., 3rd., Gonzales, F. A., Marziasz, C. M., Coetzee, G. A. and Tapscott, S. J. (1990b) De novo methylation of the MyoD1 CpG island during the establishment of immortal cell lines. Proc. Nad. Acad. Sci. USA 87: 6117-6121.
129. Jones, P. A., Rideout, W. M., 3rd., Shen, J. C., Spruck, C. H. and Tsai, Y. C. (1992) Methylation, mutation and cancer. Bioessays 14: 33-36.
130. Jost, J. P. (1993) Nuclear extracts of chicken embryos promote an active demethylation of DNA by excision repair of 5-methyldeoxycytidine. Proc. Natl. Acad. Sci. USA 90: 4684-4688.
131. Jost, J. P. and Hofsteenge, J. (1992) The repressor MDBP-2 is a member of the histone H1 family that binds preferentially in vitro and in vivo to methylated nonspecific DNA sequences. Proc. Natl. Acad. Sci. USA 89: 9499-9503.
132. Jost, J. P. and Jost, Y. C. (1994) Transient DNA demethylation in differentiating mouse myoblasts correlates with higher activity of 5-methyldeoxycytidine excision repair. J. Biol. Chem. 269: 10040-10043.
133. Jost, J. P., Siegmann, M., Sun, L. J. and Leung, R. (1995) Mechanisms of DNA demethylation in chicken embryos-purification and properties of a 5-methylcytosine-DNA glycosylase. J. Biol. Chem. 270: 9734-9739.
134. Juttermann, R., Li, E. and Jaenisch, R. (1994) 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 91: 11797-11801.
135. Kafri, T., Ariel, M., Brandeis, M., Shemer, R., Urven, L., McCarrey, J., Cedar, H. and Razin, A. (1992) Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line. Genes Dev. 6: 705-714.
136. Kafri, T., Gao, X. and Razin, A. (1993) Mechanistic aspects of genome-wide demethylation in the preimplantation mouse embryo. Proc. Natl. Acad. Sci. USA 90: 10558-10562.
137. Kaleko, M., Garcia, J. V., Osborne, W. R. and Miller, A. D. (1990) Expression of human adenosine deaminase in mice after transplantation of genetically modified bone marrow. Blood 75: 1733-1741.
138. Kanduc, D., Ghoshal, A., Quagliariello, E. and Farber, E. (1988) DNA hypomethylation in ethionine-induced rat preneoplastic hepatocyte nodules. Biochem. Biophys. Res. Commun. 150: 739-744.
139. Kaslow, D. C. and Migeon, B. R. (1987) DNA methylation stabilizes X chromosome inactivation in eutherians but not in marsupials: evidence for multistep maintenance of mammalian X dosage compensation. Proc. Natl. Acad. Sci. USA 84: 6210-6214.
140. Kass, S. U., Goddard, J. P. and Adams, R. L. (1993) Inactive chromatin spreads from a focus of methylation. Mol. Cell. Biol. 13: 7372-7379.
141. Katz, A. J. (1985) Genotoxicity of 5-azacytidine in somatic cells of Drosophila. Mutat. Res. 143: 195-199.
142. Kautiainen, T. L. and Jones, P. A. (1986) DNA methyltransferase levels in tumorigenic and nontumorigenic cells in culture. J. Biol. Chem. 261: 1594-1598.
143. Kay, G. F., Penny, G. D., Patel, D., Ashworth, A., Brockdorff, N. and Rastan, S. (1993) Expression of Xist during mouse development suggests a role in the initiation of X chromosome inactivation. Cell 72: 171-182.
144. Keith, D. H., Singer-Sam, J. and Riggs, A. D. (1986) Active X chromosome DNA is unmethylated at eight CCGG sites clustered in a guanine-plus-cytosine-rich island at the 5′ end of the gene for phosphoglycerate kinase. Mol. Cell. Biol. 6: 4122-4125.
145. Keshet, I., Yisraeli, J. and Cedar, H. (1985) Effect of regional DNA methylation on gene expression. Proc. Natl. Acad. Sci. USA 82: 2560-2564.
146. Keshet, I., Lieman-Hurwitz, J. and Cedar, H. (1986) DNA methylation affects the formation of active chromatin. Cell 44: 535-543.
147. Klimasauskas, S., Kumar, S., Roberts, R. J. and Cheng, X. (1994) HhaI methyltransferase flips its target base out of the DNA helix. Cell 76: 357-369.
148. Knight, S. J., Flannery, A. V., Hirst, M. C., Campbell, L., Christodoulou, Z., Phelps, S. R., Pointon, J., Middleton-Price, H. R., Barnicoat, A., Pembrey, M. E., Holland, J., Oostra, B. A., Bobrow, M. and Davies, K. E. (1993) Trinucleotide repeat amplification and hypermethylation of a CpG island in FRAXE mental retardation. Cell 74: 127-134.
149. Komura, J., Okada, T. and Ono, T. (1995) Repression of transient expression by DNA methylation in transcribed regions of reporter genes introduced into cultured human cells. Biochim. Biophys. Acta 1260: 73-78.
150. Kruczek, I. and Doerfler, W. (1982) The unmethylated state of the promoter/leader and 5′-regions of integrated adenovirus genes correlates with gene expression. EMBO J. 1: 409-414.
151. Kruczek, I. and Doerfler, W. (1983) Expression of the chloramphenicol acetyltransferase gene in mammalian cells under the control of adenovirus type 12 promoters: effect of promoter methylation on gene expression. Proc. Natl. Acad. Sci. USA 80: 7586-7590.
152. Kumar, S., Cheng, X., Klimasauskas, S., Mi, S., Posfai, J., Roberts, R. J. and Wilson, G. G. (1994) The DNA (cytosine-5) methyltransferases. Nucl. Acids Res. 22: 1-10.
153. Laird, P. W. and Jaenisch, R. (1994) DNA methylation and cancer. Hum. Mol. Genet. 3: 1487-1495.
154. Laird, P. W., Jacksongrusby, L., Fazeli, A., Dickinson, S. L., Jung, W. E., Li, E., Weinberg, R. A. and Jaenisch, R. (1995) Suppression of intestinal neoplasia by DNA hypomethylation. Cell 81: 197-205.
155. Lal, D., Som, S. and Friedman, S. (1988) Survival and mutagenic effects of 5-azacytidine in Escherichia coli. Mutation Res. 193: 229-236.
156. Langner, K. D., Vardimon, L., Renz, D. and Doerfler, W. (1984) DNA methylation of three 5′ C-C-G-G 3′ sites in the promoter and 5′ region inactivate the E2a gene of adenovirus type 2. Proc. Natl. Acad. Sci. USA 81: 2950-2954.
157. Lassar, A. B., Paterson, B. M. and Weintraub, H. (1986) Transfection of a DNA locus that mediates the conversion of 10T1/2 fibroblasts to myoblasts. Cell 47: 649-656.
158. Lavia, P., Ferraro, M., Micheli, A. and Olivieri, G. (1985) Effect of 5-azacytidine (5-azaC) on the induction of chromatid aberrations (CA) and sister-chromatid exchanges (SCE). Mutat. Res. 149: 463-467.
159. Lazaris-Karatzas, A., Montine, K. S. and Sonenberg, N. (1990) Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5′ cap. Nature 345: 544-547.
160. Ledley, F. D., Darlington, G. J., Hahn, T. and Woo, S. L. (1987) Retroviral gene transfer into primary hepatocytes: implications for genetic therapy of liver-specific functions. Proc. Natl. Acad. Sci. USA 84: 5335-5339.
161. Lee, Y.-W., Klein, C. B., Kargacin, B., Salinow, K., Kitahara, J., Dowjat, K., Zhitokvich, A., Christie, N. T. and Costa, M. (1995) Carcinogenic nickel silences gene expression by chromatin condensation and DNA methylation: a new model for epigenetic carcinogens. Mol. Cell. Biol. 15: 2547-2557.
162. Leonhardt, H., Page, A. W., Weier, H. U. and Bestor, T. H. (1992) A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 71: 865-873.
163. Levine, A., Cantoni, G. L. and Razin, A. (1991) Inhibition of promoter activity by methylation: possible involvement of protein mediators. Proc. Natl. Acad. Sci. USA 88: 6515-6618.
164. Levine, A., Cantoni, G. L. and Razin, A. (1992) Methylation in the preinitiation domain suppresses gene transcription by an indirect mechanism. Proc. Natl. Acad. Sci. USA 89: 10119-10123.
165. Levine, A., Yeivin, A., Ben-Asher, E., Aloni, Y. and Razin, A. (1993) Histone H1-mediated inhibition of transcription initiation of methylated templates in vitro. J. Biol. Chem. 268: 21754-21759.
166. Levine, A. J. (1993) The tumor suppressor genes. Annu. Rev. Biochem. 62: 623-651.
167. Lewis, J. D., Meehan, R. R., Henzel, W. J., Maurer-Fogy, I., Jeppesen, P., Klein, F. and Bird, A. (1992) Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell 69: 905-914.
168. Ley, T. J., DeSimone, J., Anagnou, N. P., Keller, G. H., Humphries, R. K., Turner, P. H., Young, N. S., Keller, P. and Nienhuis, A. W. (1982) 5-Azacytidine selectively increases gamma-globin synthesis in a patient with beta + thalassemia. N. Engl. J. Med. 307: 1469-1475.
169. Li, E., Bestor, T. H. and Jaenisch, R. (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69: 915-926.
170. Li, E., Beard, C. and Jaenisch, R. (1993) Role for DNA methylation in genomic imprinting. Nature 366: 362-365.
171. Liacouras, A. S. and Anderson, E. P. (1979) Uridine-cytidine kinase. i.v. Kinetics of the competition between 5-azacytidine and the two natural substrates. Mol. Pharmacol. 15: 331-340.
172. Lichtenstein, M., Keini, G., Cedar, H. and Bergman, Y. (1994) B cell-specific demethylation: a novel role for the intronic kappa chain enhancer sequence. Cell 76: 913-923.
173. Liteplo, R. G. and Kerbel, R. S. (1986) Periodate-oxidized adenosine induction of murine thymidine kinase: role of DNA methylation in the generation of tumor cell heterogeneity. Cancer Res. 46: 577-582.
174. Lock, L. F., Takagi, N. and Martin, G. R. (1987) Methylation of the Hprt gene on the inactive X occurs after chromosome inactivation. Cell 48: 39-46.
175. Long B. H., Huang, C. Y. and Pogo, A. O. (1979) Isolation and characterization of the nuclear matrix in Friend erythroleukemia cells: chromatin and hnRNA interactions with the nuclear matrix. Cell 18: 1079-1090.
176. Lowy, D. and Willumsen, B. M. (1993) Function and regulation of Ras. Annu. Rev. Biochem. 62: 851-891.
177. Lu, L. W., Chiang, G. H., Medina, D. and Randerath, K. (1976) Drug effects on nucleic acid modification. I. A specific effect of 5-azacytidine on mammalian transfer RNA methylation in vivo. Biochem. Biophys. Res. Commun. 68: 1094-10101.
178. Lubet, R. A., Kouri, R. E., Curren, R. A., Putman, D. L. and Schechtman, L. M. (1990) Induction of mutagenesis and transformation in BALB/c-3T3 clone A31-1 cells by diverse chemical carcinogens. Environ. Mol. Mutagen. 16: 13-20.
179. Lyon, M. F. (1992) Some milestones in the history of x-chromosome inactivation. Annu. Rev. Genet. 26: 17-28.
180. Macleod, D., Charlton, J., Mullins, J. and Bird, A. P. (1994) Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes &. Dev. 8: 2282-2292.
181. MacLeod, A. R. and Szyf, M. (1995) Expression of an antisense to the DNAmethyltransferase mRNA induces DNA demethylation and inhibits tumorigenesis. J. Biol. Chem. 270: 8037-8043.
182. MacLeod, A. R., Rouleau, J. and Szyf, M. (1995) Regulation of DNA methylation by the Ras signaling pathway. J. Biol. Chem. 270: 11327-11337.
183. Magewu, A. N. and Jones, P. A. (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: 4225-4232.
184. Makos, M., Nelkin, B. D., Lerman, M. I., Latif, F., Zbar, B. and Baylin, S. B. (1992) Distinct hypermethylation patterns occur at altered chromosome loci in human lung and colon cancer. Proc. Natl. Acad. Sci. USA 89: 1929-1933.
185. Makos-Wales, M., Biel, M. A., El Deiry, W., Nelkin, B. D., Issa, J.-P., Cavenee, W. K., Kuerbitz, S. J. and Baylin, S. B. (1995) p53 activates expression of HIC-1, a new candidate tumor suppressor gene on 17p13.3 Nature Med. 1: 570-577.
186. Matsuda, M. (1990) Comparison of the incidence of 5-azacytidine-induced exencephaly between MT/Hokldr and Slc:ICR mice. Teratology 41: 147-154.
187. Mavilio, F., Giampaolo, A., Care, A., Migliaccio, G., Calandrini, M., Russo, G., Pagliardi, G. L., Mastroberardino, G., Marinucci, M. and Peschle, C. (1983) Molecular mechanisms of human hemoglobin switching: selective undermethylation and expression of globin genes in embryonic, fetal, and adult erythroblasts. Proc. Natl. Acad. Sci. USA 80: 6907-6911.
188. Maxam, A. M. and Gilbert, W. (1980) Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 65: 499-560.
189. McGrath, J. and Solter, D. (1984) Completion of mouse embryo-genesis requires both the maternal and paternal genomes. Cell 37: 179-183.
190. Mellon, S. H., Miller, W. L., Bair, S. R., Moore, C. C., Vigne, J. L. and Weiner, R. I. (1994) Steroidogenic adrenocortical cell lines produced by genetically targeted tumorigenesis in transgenic mice. Mol. Endocrinol. 8: 97-108.
191. Merlo, A., Herman, J. G., Mao, L., Lee, D. J., Gabrielson, E., Burger, P., Baylin, S. B. and Sidransky, D. (1995) 5′ CpG island methylation is associated with transcriptional silencing of the tumor suppressor p16/CDKN2/MTS1 in human cancers. Nature Med. 1: 686-692.
192. Messer, W., Bellekes, U. and Lother, H. (1985) Effect of dam methylation on the activity of the E. coli replication origin, oriC. EMBO J. 4: 1327-1332.
193. Migeon, B. R. (1994) X-chromosome inactivation: molecular mechanisms and genetic consequences. Trends Genet. 10: 230-235.
194. Mixon, J. C. and Dev, V. G. (1983) Fragile X expression is decreased by 5-azacytidine and S-adenosylhomocysteine. Am. J. Hum. Genet. 35: 1270-1275.
195. Mohandas, T., Sparkes, R. S. and Shapiro, L. J. (1981) Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation. Science 211: 393-396.
196. Momparler, R. L., Momparler, L. F. and Samson, J. (1984) Comparison of the antileukemic activity of 5-AZA-2′-deoxycytidine, 1-beta-D-arabinofuranosylcytosine and 5-azacytidine against L1210 leukemia. Leuk. Res. 8: 1043-1049.
197. Monk, M., Boubelik, M. and Lehnert, S. (1987) Temporal and regional changes in DNA methylation in the embryonic, extra-embryonic and germ cell lineages during mouse embryo development. Development 99: 371-382.
198. Monk, M., Adams, R. L. and Rinaldi, A. (1991) Decrease in DNA methylase activity during preimplantation development in the mouse. Development 112: 189-192.
199. Motoji, T., Hoang, T., Tritchler, D. and McCulloch, E. A. (1985) The effect of 5-azacytidine and its analogues on blast cell renewal in acute myeloblastic leukemia. Blood 65: 894-901.
200. Mummaneni, P., Bishop, P. L. and Turker, M. S. (1993) A cis-acting element accounts for a conserved methylation pattern upstream of the mouse adenine phosphoribosyltransferase gene. J. Biol. Chem. 268: 552-558.
201. Mummaneni, P., Walker, K. A., Bishop, P. L. and Turker, M. S. (1995) Epigenetic gene inactivation induced by a cis-acting methylation center. J. Biol. Chem. 270: 788-792.
202. Nelkin, B. D., Przepiorka, D., Burke, P. J., Thomas, E. D. and Baylin, S. B. (1991) Abnormal methylation of the calcitonin gene marks progression of chronic myelogenous leukemia. Blood 77: 2431-2434.
203. Noda, M., Ko, M., Ogura, A., Liu, D. G., Amano, T., Takano, T. and Ikawa, Y. (1985) Sarcoma viruses carrying ras oncogenes induce differentiation-associated properties in a neuronal cell line. Nature 318: 73-75.
204. Norris, D. P., Patel, D., Kay, G. F., Penny, G. D., Brockdorff, N., Sheardown, S. A. and Rastan, S. (1994) Evidence that random and imprinted Xist expression is controlled by preemptive methylation. Cell 77: 41-51.
205. Nur, I., Szyf, M., Razin, A., Glaser, G., Rottem, S. and Razin, S. (1985) Procaryotic and eucaryotic traits of DNA methylation in spiroplasmas (mycoplasmas). J. Bacteriol. 164: 19-24.
206. Ogawa, O., Eccles, M. R., Szeto, J., McNoe, L. A., Yun, K., Maw, M. A., Smith, P. J. and Reeve, A. E. (1993) Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour. Nature 362: 749-751.
207. Ohtani-Fujita, N., Fujita, T., Aoike, A., Osifchin, N. E., Robbins, P. D. and Sakai, T. (1993) CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene. Oncogene 8: 1063-1067.
208. Orend, G., Kuhlmann, I. and Doerfler, W. (1991) Spreading of DNA methylation across integrated foreign (adenovirus type12) genomes in mammalian cells. J. Virol. 65: 4301-4308.
209. Orend, G., Knoblauch, M., Kammer, C., Tjia, S. T., Schmitz, B., Linkwitz, A., Meyer, G., Maas, J. and Doerfler, W. (1995) The initiation of de novo methylation of foreign DNA integrated into a mammalian genome is not exclusively targeted by nucleotide sequence. J. Virol. 69: 1226-1242.
210. Orkin, S. H., Kazazian, H. H., Jr., Antonarakis, S. E., Goff, S. C., Boehm, C. D., Sexton, J. P., Waber, P. G. and Giardina, P. J. (1982) Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymorphisms in human beta-globin gene cluster. Nature 296: 627-631.
211. Osgood, C. J. and Seward, S. M. (1989) 5-Azacytidine induces sex chromosome loss and interchange in immature germ cells of Drosophila mei-9 males. Env. Mol. Mutagen. 14: 135-145.
212. Osterman, D. G., DePillis, G. D., Wu, J. C., Matsuda, A. and Santi, D. V. (1988) 5-Fluorocytosine in DNA is a mechanism-based inhibitor of HhaI methylase. Biochemistry 27: 5204-5210.
213. Ottaviano, Y. L., Issa, J. P., Pari, F. F., Smith, H. S., Baylin, S. B. and Davidson, N. E. (1994) Methylation of the estrogen receptor gene CpG island marks loss of estrogen receptor expression in human breast cancer cells. Cancer Res. 54: 2552-2555.
214. Palmer, T. D., Rosman, G. J., Osborne, W. R. and Miller, A. D. (1991) Genetically modified skin fibroblasts persist long after transplantation but gradually inactivate introduced genes. Proc. Nad. Acad. Sci. USA 88: 1330-1334.
215. Papadopoulos, V., Kamtchouing, P., Drosdowsky, M. A. and Carreau, S. (1987) Effects of the transmethylation inhibitor S-adenosyl-homocysteine and of the methyl donor S-adenosyl-methionine on rat Leydig cell function in vitro. J. Steroid Biochem. 26: 93-98.
216. Paranjape, S. M., Kamakaka, R. T. and Kadonaga, J. T. (1994) Role of chromatin structure in the regulation of transcription by RNA polymerase II. Annu. Rev. Biochem. 63: 265-297.
217. Paroush, Z., Keshet, I., Yisraeli, J. and Cedar, H. (1990) Dynamics of demethylation and activation of the alpha-actin gene in myoblasts. Cell 63: 1229-1237.
218. Pawlak, A., Bryans, M. and Jost, J.-P. (1991) An avian 40 KDa nucleo-protein binds preferentially to a promoter sequence containing one single pair of methylated CpG. Nucl. Acids Res. 19: 1029-1034.
219. Peterson, K. and Sapienza, C. (1993) Imprinting the genome: imprinted genes, imprinting genes, and a hypothesis. Annu. Rev. Genet. 27: 7-31.
220. Pfeifer, G. P., Steigerwald, S. D., Mueller, P. R., Wold, B. and Riggs, A. D. (1989) Genomic sequencing and methylation analysis by ligation mediated PCR. Science 246: 810-813.
221. Pfeifer, G. P., Steigerwald, S. D., Hansen, R. S., Gartler, S. M. and Riggs, A. D. (1990a) Polymerase chain reaction-aided genomic sequencing of an X chromosome-linked CpG island: methylation patterns suggest clonal inheritance, CpG site autonomy, and an explanation of activity state stability. Proc. Nad. Acad. Sci. USA 87: 8252-8256.
222. Pfeifer, G. P., Tanguay, R. L., Steigerwald, S. D. and Riggs, A. D. (1990b) In vivo footprint and methylation analysis by PCR-aided genomic sequencing: comparison of active and inactive X chromosomal DNA at the CpG island and promoter of human PGK-1. Genes Dev. 4:1 277-1287.
223. Pinto, A. and Zagonel, V. (1993) 5-Aza-2′-deoxycytidine (Decitabine) and 5-azacytidine in the treatment of acute myeloid leukemias and myelodysplastic syndromes: past, present and future trends. Leukemia 7 (Suppl. 1): 51-60.
224. Platt, O. S. (1995) Sickle cell paths converge on hydroxyurea. Nature Med. 1: 307-308.
225. Platt, O. S., Orkin, S. H., Dover, G., Beardsley, G. P., Miller, B. and Nathan, D. G. (1987) Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. J. Clin. Invest. 74: 652-656.
226. Poot, M., Koehler, J., Rabinovitch, P. S., Hoehn, H. and Priest, J. H. (1990) Cell kinetic disturbances induced by treatment of human diploid fibroblasts with 5-azacytidine indicate a major role for DNA methylation in the regulation of the chromosome cycle. Hum. Genet. 84: 258-262.
227. Prendergast, G. C. and Ziff, E. B. (1991) Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region. Science 251: 186-189.
228. Prendergast, G. C., Lawe, D. and Ziff, E. B. (1991) Association of Myn, the murine homolog of max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation. Cell 65: 395-407.
229. Quagliana, J. M., O'Bryan, R. M., Baker, L., Gottlieb, J., Morrison, F. S., Eyre, H. J., Tucker, W. G. and Costanzi, J. (1977) Phase II study of 5-azacytidine in solid tumors. Cancer Treat. Rep. 61: 51-54.
230. Rao, P. M., Antony, A., Rajalakshmi, S. and Sarma, D. S. (1989) Studies on hypomethylation of liver DNA during early stages of chemical carcinogenesis in rat liver. Carcinogenesis 10: 933-937.
231. Ray, J. S., Harbison, M. L., McClain, R. M. and Goodman, J. I. (1994) Alterations in the methylation status and expression of the raf oncogene in phenobarbital-induced and spontaneous B6C3F1 mouse live tumors. Mol. Carcinog. 9: 155-166.
232. Razin, A. and Cedar, H. (1977) Distribution of 5-methylcytosine in chromatin. Proc. Natl. Acad. Sci. USA 74: 2725-2728.
233. Razin, A. and Kafri, T. (1994) DNA methylation from embryo to adult. Prog. Nucl. Acid Res. Mol. Biol. 48: 53-81.
234. Razin, A. and Riggs, A. D. (1980) DNA methylation and gene function. Science 210: 604-610.
235. Razin, A. and Szyf, M. (1984) DNA methylation patterns. Formation and function. Biochim. Biophys. Acta 782: 331-342.
236. Razin, A., Webb, C., Szyf, M., Yisraeli, J., Rosenthal, A., Naveh-Many, T., Sciaky-Gallili, N. and Cedar, H. (1984) Variations in DNA methylation during mouse cell differentiation in vivo and in vitro. Proc. Natl. Acad. Sci. USA 81: 2275-2279.
237. Razin, A., Feldmesser, E., Kafri, T. and Szyf, M. (1985) Cell specific DNA methylation patterns; formation and a nucleosome locking model for their function. Prog. Clinic. Biol. Res. 198: 239-253.
238. Razin, A., Szyf, M., Kafri, T., Roll, M., Giloh, H., Scarpa, S., Carotti, D. and Cantoni G. L. (1986) Replacement of 5-methylcytosine by cytosine: a possible mechanism for transient DNA demethylation during differentiation. Proc. Natl. Acad. Sci. USA 83: 2827-2831.
239. Richard-Foy, H. and Hager, G. L. (1987) Sequence-specific positioning of nucleosomes over the steroid-inducible MMTV promoter. EMBO J. 6: 2321-2328.
240. Rideout, W. M., 3rd., Coetzee, G. A., Olumi, A. F. and Jones, P. A. (1990) 5-Methylcytosine as an endogenous mutagen in the human LDL receptor and p53 genes. Science 249: 1288-1290.
241. Rideout, W. M., 3rd., Eversole-Cire, P., Spruck, C. H., 3rd., Hustad, C. M., Coetzee, G. A., Gonzales, F. A. and Jones, P. A. (1994) Progressive increases in the methylation status and heterochromatinization of the myoD CpG island during oncogenic transformation. Mol. Cell. Biol. 14: 6143-6152.
242. Riggs, A. D. (1975) X inactivation, differentiation and DNA methylation. Cytogenet. Cell Genet. 14: 9-25.
243. Riley, D. J., Lee, E. Y.-H. and Lee, W.-H. (1994) The retinoblastoma gene. Annu. Rev. Cell. Biol. 10: 1-29.
244. Rimoldi, D., Srikantan, V., Wilson, V. L., Bassin, R. H. and Samid, D. (1991) Increased sensitivity of nontumorigenic fibroblasts expressing ras or myc oncogenes to malignant transformation induced by 5-aza-2′-deoxycytidine. Cancer Res. 51: 324-330.
245. Rosen, M. B., House, H. S., Francis, B. M. and Chernoff, N. (1990) Teratogenicity of 5-azacytidine in the Sprague-Dawley rat. J. Toxicol. Environ. Health 29: 201-210.
246. Rouleau, J., Tanigawa, G. and Szyf, M. (1992) The mouse DNA methyltransferase 5′-region. A unique housekeeping gene promoter. J. Biol. Chem. 267: 7368-7377.
247. Rouleau, J., MacLeod, A. R. and Szyf, M. (1995) Regulation of the DNA methyltransferase by the Ras-AP-1 signaling pathway. J. Biol. Chem. 270: 1595-1601.
248. Royer-Pokora, B. and Schneider, S. (1992) Wilms' tumor-specific methylation pattern in 11p13 detected by PFGE. Genes Chromosom. Cancer 5: 132-140.
249. Russell, D. W. and Zinder, N. D. (1987) Hemimethylation prevents DNA replication in E. coli. Cell 50: 1071-1079.
250. Santi, D. V., Norment, A. and Garrett, C. E. (1984) Covalent bond formation between a DNA-cytosine methyltransferase and DNA containing 5-azacytosine. Proc. Nad. Acad. Sci. USA 81: 6993-6997.
251. Santoro, R., D'Erme, M., Mastrantonio, S., Reale, A., Marenzi, S., Saluz, H. P., Strom, R. and Caiafa, P. (1995) Binding of histone H1e-c variants to CpG-rich DNA correlates with the inhibitory effect on enzymic DNA methylation. Biochem. J. 305: 739-744.
252. Sapienza, C., Peterson, A. C., Rossant, J. and Balling, R. (1987) Degree of methylation of transgenes is dependent on gamete of origin. Nature 328: 251-254.
253. Sapienza, C., Paquette, J., Tran, T. H. and Peterson A. (1989) Epigenetic and genetic factors affect transgene methylation imprinting. Development 107: 165-168.
254. Sasaki, H., Jones, P. A., Chaillet, J. R., Ferguson-Smith, A. C., Barton, S. C., Reik, W. and Surani, M. A. (1992) Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene. Genes Dev. 6: 1843-1856.
255. Schlessinger, J. and Ullrich, A. (1992) Growth factor signaling by receptor tyrosine kinases. Neuron. 9: 383-391.
256. Scrable, H., Cavenee, W., Ghavimi, F., Lovell, M., Morgan, K. and Sapienza, C. (1989) A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting. Proc. Natl. Acad. Sci. USA 86: 7480-7484.
257. Sengupta, P. K., Lavelle, D. and DeSimone, J. (1994) Increased binding of Sp1 to the gamma-globin gene promoter upon site-specific cytosine methylation. Am. J. Hematol. 46: 169-172.
258. Shemer, R., Eisenberg, S., Breslow, J. L. and Razin, A. (1991) Methylation patterns of the human apoA-I/C-III/A-IV gene cluster in adult and embryonic tissues suggest dynamic changes in methylation during development. J. Biol. Chem. 266: 23676-23681.
259. Shen, C. K. and Maniatis, T. (1980) Tissue-specific DNA methylation in a cluster of rabbit beta-like globin genes. Proc. Natl. Acad. Sci. USA 77: 6634-6638.
260. Shen, J. C., Rideout, W. M., 3rd. and Jones, P. A. (1992) High frequency mutagenesis by a DNA methyltransferase. Cell 71: 1073-1080.
261. Silva, A. J. and White, R. (1988) Inheritance of allelic blueprints for methylation patterns. Cell 54: 145-52.
262. Simon, D., Stuhlmann, H., Jahner, D., Wagner, H., Werner, E. and Jaenisch, R. (1983) Retrovirus genomes methylated by mammalian but not bacterial methylase are noninfectious. Nature 304: 275-277.
263. Singer, J., Roberts-Ems, J. and Riggs, A. D. (1979) Methylation of mouse liver DNA studied by means of the restriction enzymes msp I and hpa II. Science 203: 1019-1021.
264. Singer-Sam, J., Grant, M., LeBon, J. M., Okuyama, K., Chapman, V., Monk, M., and Riggs, A. D. (1990a) Use of a Hpall-polymerase chain reaction assay to study DNA methylation in the Pgk-1 CpG island of mouse embryos at the time of X-chromosome inactivation. Mol. Cell. Biol. 10: 4987-4989.
265. Singer-Sam, J., Robinson, M. O., Bellve, A. R., Simon, M. I. and Riggs, A. D. (1990) Measurement by quantitative PCR of changes in HPRT, PGK-1, PGK-2, APRT, MTase, and Zfy gene transcripts during mouse spermatogenesis. Nucl. Acids Res. 18: 1255-1259.
266. Smith, D. W., Garland, A. M., Herman, G., Enns, R. E., Baker, T. A. and Zyskind, J. W. (1985) Importance of state of methylation of oriC GATC sites in initiation of DNA replication in Escherichia coli. EMBO J. 4: 1319-1326.
267. Snyder, R. D. and Lachmann, P. J. (1989) Differential effects of 5-azacytidine and 5-azadeoxycytidine on cytotoxicity, DNA-strand breaking and repair of X-ray-induced DNA damage in HeLa cells. Mutat. Res. 226: 185-190.
268. Soultanas, P., Andrews, P. D., Burton, D. R. and Hornby, D. P. (1993) Modulation of human DNA methyltransferase activity and mRNA levels in the monoblast cell line U937 induced to differentiate with dibutyryl cyclic AMP and phorbol ester. J. Mol. Endocrinol. 11: 191-200.
269. Stark, M., Bilzer, T., Inoue, N. and Wechsler, W. (1989) Influence of 5-azacytidine on differentiation and growth in rat nervous system tumor cell lines. Neurotoxicol. Teratol. 11: 557-561.
270. Stein, R., Gruenbaum, Y., Pollack, Y., Razin, A. and Cedar, H. (1982a) Clonal inheritance of the pattern of DNA methylation in mouse cells. Proc. Natl. Acad. Sci. USA 79: 61-65.
271. Stein, R., Razin, A. and Cedar, H. (1982b) In vitro methylation of the hamster adenine phosphoribosyltransferase gene inhibits its expression in mouse L cells. Proc. Natl. Acad. Sci. USA 79: 3418-3422.
272. Stoger, R., Kubicka, P., Liu, C. G., Kafri, T., Razin, A., Cedar, H. and Barlow, D. P. (1993) Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal. Cell 73: 61-71.
273. Sutcliffe, J. S., Nelson, D. L., Zhang, F., Pieretti, M., Caskey, C. T., Saxe, D. and Warren, S. T. (1992) DNA methylation represses FMR-1 transcription in fragile X syndrome. Hum. Mol. Genet. 1: 397-400.
274. Sutter, D. and Doerfler, W. (1980) Methylation of integrated adeno-virus type 12 DNA sequences in transformed cells is inversely correlated with viral gene expression. Proc. Natl. Acad. Sci. USA 77: 253-256.
275. Swain, J. L., Stewart, T. A. and Leder, P. (1987) Parental legacy determines methylation and expression of an autosomal transgene: a molecular mechanism for parental imprinting. Cell 50: 719-727.
276. Szyf, M. (1991) DNA methylation patterns: an additional level of information? Biochem. Cell Biol. 69: 764-767.
277. Szyf, M. (1994) DNA methylation properties: consequences for pharmacology. Trends Pharmacol. Sci. 15: 233-238.
278. Szyf, M., Avraham-Haetzni, K., Reifman, A., Shlomai, J., Kaplan, F., Oppenheim, A. and Razin A. (1984) DNA methylation pattern is determined by the intracellular level of the methylase. Proc. Natl. Acad. Sci. USA 81: 3278-3282.
279. Szyf, M., Eliasson, L., Mann, Y., Klein, G. and Razin, A. (1985) Cellular and viral DNA hypomethylation associated with induction of Epstein-Barr virus lytic cycle. Proc. Natl. Acad. Sci. USA 82: 8090-8094.
280. Szyf, M., Schimmer, B. P. and Seidman, J. G. (1989) Nucleotide-sequence-specific de novo methylation in a somatic murine cell line. Proc. Natl. Acad. Sci. USA 86: 6853-6857.
281. Szyf, M., Milstone, D. S., Schimmer, B. P., Parker, K. L. and Seidman, J. G. (1990a) cis Modification of the steroid 21-hydroxylase gene prevents its expression in the Y1 mouse adrenocortical tumor cell line. Mol. Endocrinol. 4: 1144-1152.
282. Szyf, M., Tanigawa, G. and McCarthy, P. L., Jr. (1990b) A DNA signal from the Thy-1 gene defines de novo methylation patterns in embryonic stem cells. Mol. Cell. Biol. 10: 4396-4340.
283. Szyf, M., Bozovic, V. and Tanigawa, G. (1991) Growth regulation of mouse DNA methyltransferase gene expression. J. Biol. Chem. 266: 10027-10030.
284. Szyf, M., Rouleau, J., Theberge, J. and Bozovic, V. (1992) Induction of myogenic differentiation by an expression vector encoding the DNA methyltransferase cDNA sequence in the antisense orientation. J. Biol. Chem. 267: 12831-12836.
285. Szyf, M., Theberge, J. and Bozovic, V. (1995) Ras induces a general DNA demethylation activity in mouse embryonal P19 cells. J. Biol. Chem. 270: 12690-12696.
286. Takeuchi, I. K. and Takeuchi, Y. K. (1985) 5-Azacytidine-induced exencephaly in mice. J. Anat. 140: 403-412.
287. Tamame, M., Antequera, F., Villanueva, J. R. and Santos, T. (1983) High-frequency conversion to a "fluffy" developmental phenotype in Aspergillus spp. by 5-azacytidine treatment: evidence for involvement of a single nuclear gene. Mol. Cell. Biol. 3: 2287-2297.
288. Taniguchi, T., Sullivan, M. J., Ogawa, O. and Reeve, A. E. (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: 2159-2163.
289. Tasheva, E. S. and Roufa, D. J. (1994) Densely methylated DNA islands in mammalian chromosomal replication origins. Mol. Cell. Biol. 14: 5636-5644.
290. Taylor, S. M. (1993) 5-Aza-2′-deoxycytidine: cell differentiation and DNA methylation. Leukemia 7: 3-8.
291. Taylor, S. M. and Jones, P. A. (1979) Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell 17: 771-779.
292. Tollefsbo, T. O. and Hutchison, C. A. (1995) Mammalian DNA (cytosine-5-)-methyltransferase expressed in Escherichia coli, purified and characterized. J. Biol. Chem. 270: 18543-18550.
293. Tosi, L., Aniello, F., Geraci, G. and Branno, M. (1995) DNA methyltransferase activity in the early stages of a sea urchin embro. Evidence of differential control. FEBS Lett. 361: 115-117.
294. Toth, M., Muller, U and Doerfler, W. (1990) Establishment of de novo DNA methylation patterns. Transcription factor binding and deoxycytidine methylation at CpG and nonCpG sequences in an integrated adenovirus promoter. J. Mol. Biol. 214: 673-683.
295. Trasler, J. M., Alcivar, A. A., Hake, L. E., Bestor, T. and Hecht, N. B. (1992) DNA methyltransferase is developmentally expressed in replicating and nonreplicating male germ cells. Nucl. Acids Res. 25: 2541-2545.
296. Tsukiyama, T., Becker, P. B. and Wu, C. (1994) ATP-dependent nucleosome disruption at a heat-shock promoter mediated by binding of GAGA transcription factor. Nature 367: 525-532.
297. Turker, M. S., Swisshelm, K., Smith, A. C. and Martin, G. M. (1989) A partial methylation profile for a CpG site is stably maintained in mammalian tissues and cultured cell lines. J. Biol. Chem. 264: 11632-11636.
298. Turker, M. S., Mummaneni, P. and Bishop, P. L. (1991) Region-and cell type-specific de novo DNA methylation in cultured mammalian cells. Somat. Cell Mol. Genet. 17: 151-157.
299. Vairapandi, M. and Duker, N. J. (1993) Enzymic removal of 5-methylcytosine from DNA by a human glycosylase. Nucl. Acids Res. 21: 5323-5327.
300. Vardimon, L., Kressmann, A., Cedar, H., Maechler, M. and Doerfler, W. (1982) Expression of a cloned adenovirus gene is inhibited by in vitro methylation. Proc. Natl. Acad. Sci. USA 79: 1073-1077.
301. Vedel, M., Robert-Gero, M., Legraverend, M., Lawrence, F. and Lederer, E. (1978) Inhibition of tR. N.A methylation in vitro and in whole cells by an oncostatic S-adenosyl-homocysteine (SAH) analogue: 5′-deoxy 5′-S-isobutyladenosine (SIBA). Nucl. Acids Res. 5: 2979-2989.
302. Vertino, P. M., Spillare, E. A., Harris, C. C. and Baylin, S. B. (1993) Altered chromosomal methylation patterns accompany oncogene-induced transformation of human bronchial epithelial cells. Cancer Res. 53: 1684-1689.
303. Vertino, P. M., Issa, J. P., Pereirasmith, O. M. and Baylin, S. B. (1994) Stabilization of DNA methyltransferase level and CpG island hypermethylation precede SV40-induced immortilization of human fibroblasts. Cell Growth Differ. 5: 1395-1402.
304. Von Hoff, D. D., Slavik, M. and Muggia, F. M. (1976) 5-Azacytidine. A new anticancer drug with effectiveness in acute myelogenous leukemia. Ann. Intern. Med. 85: 237-245.
305. Vorce, R. L. and Goodman, J. I. (1989) Altered methylation of ras oncogenes in benzidine-induced B6C3F1 mouse liver tumors. Toxicol. Appl. Pharmacol. 100: 398-410.
306. Waalwijk, C. and Flavell, R. A. (1978a) MspI, an isoschizomer of hpaII which cleaves both unmethylated and methylated hpaII sites. Nucl. Acids Res. 5: 3231-3236.
307. Waalwijk, C. and Flavell, R. A. (1978b) DNA methylation at a CCGG sequence in the large intron of the rabbit beta-globin gene: tissue-specific variations. Nucl. Acids Res. 5: 4631-4634.
308. Wahlfors, J., Hiltunen, H., Heinonen, K., Hamalainen, E., Alhonen, L. and Janne, J. (1992) Genomic hypomethylation in human chronic lymphocytic leukemia. Blood 80: 2074-2080.
309. Wainfan, E., Dizik, M., Stender, M. and Christman, J. K. (1989) Rapid appearance of hypomethylated DNA in livers of rats fed cancer-promoting, methyl-deficient diets. Cancer Res. 49: 4094-4097.
310. Walker, C. and Nettesheim, P. (1989) In vitro neoplastic progression of rat tracheal epithelial cells transformed by diverse carcinogens. Cancer Res. 49: 4427-4430.
311. Walker, C., Matthews, A. M. and Shay, J. W. (1987) Suppression of tumorigenicity mediated by 5-azacytidine and associated with increased chromosome number. J. Natl. Cancer Inst. 78: 695-700.
312. Wallace, R. E., Lindh, D. and Durr, F. E. (1989) Arabinofuranosyl-5-azacytosine: activity against human tumors in athymic mice. Cancer Chemother. Pharmacol. 25: 117-123.
313. Weih, F., Nitsch, D., Reik, A., Schutz, G. and Becker, P. B. (1991) Analysis of CpG methylation and genomic footprinting at the tyrosine aminotransferase gene: DNA methylation alone is not sufficient to prevent protein binding in vivo. EMBO J. 10: 2559-2567.
314. Weinberg, R. A. (1985) The action of oncogenes in the cytoplasm and nucleus. Science 230: 770-776.
315. Weiss, A. J., Metter, G. E., Nealon, T. F., Keanan, J. P., Ramirez, G., Swaiminathan, A., Fletcher, W. S., Moss, S. E. and Manthei, R. W. (1977) Phase II study of 5-azacytidine in solid tumors. Cancer Treat. Rep. 61: 55-58.
316. Weisshaar, B., Langner, K. D., Juttermann, R., Muller, U., Zock, C., Klimkait, T. and Doerfler, W. (1988) Reactivation of the methylation-inactivated late E2A promoter of adenovirus type 2 by E1A (13 S) functions. J. Mol. Biol. 202: 255-270.
317. Weksberg, R., Shen, D. R., Fei, Y. L., Song, Q. L. and Squire J. (1993) Disruption of insulin-like growth factor 2 imprinting in Beckwith-Wiedemann syndrome. Nature Genet. 5: 143-150.
318. Wilks, A., Seldran, M. and Jost, J. P. (1984) An estrogen-dependent demethylation at the 5′ end of the chicken vitellogenin gene is independent of DNA synthesis. Nucl. Acids Res. 12: 1163-1177.
319. Williams, D. A., Orkin, S. H. and Mulligan, R. C. (1986) Retrovirus-mediated transfer of human adenosine deaminase gene sequences into cells in culture and into murine hematopoietic cells in vivo. Proc. Natl. Acad. Sci. USA 83: 2566-2570.
320. Wilson,V. L., Jones, P. A. and Momparler, R. L. (1983) Inhibition of DNA methylation in L1210 leukemic cells by 5-aza-2′-deoxycytidine as a possible mechanism of chemotherapeutic action. Cancer Res. 43: 3493-3496.
321. Woodcock, D. M., Crowther, P. J. and Diver, W. P. (1987) The majority of methylated deoxycytidines in human DNA are not in the CpG dinucleotide. Biochem. Biophys. Res. Commun. 145: 888-894.
322. Woodcock, D. M., Crowther, P. J., Jefferson, S. and Diver, W. P. (1988) Methylation at dinucleotides other than CpG: implications for human maintenance methylation. Gene 74: 151-152.
323. Wu, J. C. and Santi, D. V. (1985) On the mechanism and inhibition of DNA cytosine methyltransferases. Prog. Clin. Biol. Res. 198: 119-129.
324. Wu, J., Issa, J. P., Herman, J., Bassett, D. E., Jr., Nelkin, B. D. and Baylin, S. B. (1993) Expression of an exogenous eukaryotic DNA methyltransferase gene induces transformation of NIH 3T3 cells. Proc. Natl. Acad. Sci. USA 90: 8891-8895.
325. Xu, G., Flynn, J., Glickman, J. F. and Reich, N. O. (1995) Purification and stabilization of mouse DNA methyltransferase. Biochem. Biophys. Res. Commun. 207: 544-551.
326. Yen, R. W., Vertino, P. M., Nelkin, B. D., Yu, J. J., el-Deiry, W., Cumaraswamy, A., Lennon, G. G., Trask, B. J., Celano, P. and Baylin, S. B. (1992) Isolation and characterization of the cDNA encoding human DNA methyltransferase. Nucl. Acids Res. 20: 2287-2291.
327. Yisraeli, J. and Szyf, M. (1984) The pattern of methylation of eukaryotic genes. In: DNA Methylation and its Biological Significance, pp. 353-378, Razin, A., Cedar, H. and Riggs, A. D. (eds.) Springer Verlag Inc., New York.
328. Yisraeli, J., Frank, D., Razin, A. and Cedar, H. (1988) Effect of in vitro DNA methylation on beta-globin gene expression. Proc. Natl. Acad. Sci. USA 85: 4638-4642.
329. Zhang, X. Y., Jabrane-Ferrat, N., Asiedu, C. K., Samac, S., Peterlin, B. M. and Ehrlich, M. (1993) The major histocompatibility complex class II promoter-binding protein RFX (NF-X) is a methylated DNA-binding protein. Mol. Cell. Biol. 13: 6810-6818.
330. Zimmermann, F. K. and Scheel, I. (1984) Genetic effects of 5-azacytidine in Saccharomyces cerevisiae. Mutat. Res. 139: 21-24.
331. Zuccotti, M. and Monk, M. (1995) Methylation of the mouse Xist gene in sperm and eggs correlates with imprinted Xist expression and paternal X-inactivation. Nature Genet. 9: 316-320.