Molecular and enzymatic profiles of mammalian DNA methyltransferases: Structures and targets for drugs

Current Medicinal Chemistry

Volumn 17, Issue 33, 2010, Pages 4052-4071

  Xu, F ^a   Mao, C ^a   Ding, Y ^a   Rui, C ^a   Wu, L ^a   Shi, A ^a   Zhang, H ^a   Zhang, L ^b   Xu, Z ^a,b  

^a SOOCHOW UNIVERSITY   (China)

^b LOMA LINDA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

DNA methyltransferase; Enzyme catalysis; Epigenetics; Protein DNA interactions

Indexed keywords

CYTOSINE; DNA METHYLTRANSFERASE; DNA METHYLTRANSFERASE 1; DNA METHYLTRANSFERASE 3A; DNA METHYLTRANSFERASE 3B; DOUBLE STRANDED DNA; METHANEARSONATE DISODIUM;

ARTICLE; CARBOXY TERMINAL SEQUENCE; CHROMOSOME; DNA METHYLATION; DNA SEQUENCE; EPIGENETICS; GENE MAPPING; HETEROCHROMATIN; HUMAN; MAMMAL; NONHUMAN; POSITION; PROTEIN VARIANT;

ANIMALS; DNA; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DNA METHYLATION; EPIGENESIS, GENETIC; HUMANS; MAMMALS; MOLECULAR TARGETED THERAPY; REGULATORY SEQUENCES, NUCLEIC ACID;

EID: 79251494766     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986710793205372     Document Type: Article

References (152)

1. Hochkiss, R.D. The quantitative separation of purine, pyrimidines and nucleoside by paper chromatography. J. Biol. Chem., 1948, 168, 315-332.
2. Reik, W.; Walter, J. Genomic imprinting: Parental influence on the genome. Nat. Rev. Genet., 2001, 2(1), 21-32.
3. Robertson, K.D. DNA methylation and human disease. Nat. Rev. Genet., 2005, 6(8), 597-610.
4. Latham, K.E. Epigenetic modification and imprinting of the mammalian genome during development. Curr. Top. Dev. Biol., 1999, 43, 1-49.
5. Dolinoy, D.C.; Weidman, J.R.; Jirtle, R.L. Epigenetic gene regulation: Linking early developmental environment to adult disease. Reprod. Toxicol., 2007, 23(3), 297-307.
6. Hermann, A.; Gowher, H.; Jeltsch, A. Biochemistry and biology of mammalian DNA methyltransferases. Cell Mol. Life Sci., 2004, 61(19-20), 2571-2587.
7. Turek-Plewa, J.; Jagodziński, P.P. The role of mammalian DNA methyltransferases in the regulation of gene expression. Cell Mol. Biol. Lett., 2005, 10(4), 631-647.
8. Bogdanović, O.; Veenstra, G.J. DNA methylation and methyl-CpG binding proteins: Developmental requirements and function. Chromosoma, 2009, 118(5), 549-565.
9. Bestor, T.H.; Ingram, V.M. Growth-dependent expression of multiple species of DNA methyltransferase in murine erythroleukemia cells. Proc. Natl. Acad. Sci., 1985, 82(9), 2674-2678.
10. Bestor, T.; Laudano, A.; Mattaliano, R.; Ingram, V. 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., 1988, 203(4), 971-983.
11. Okano, M.; Xie, S.; Li, E. Cloning and characterization of a family of novel mammalian DNA (cytosine-5) methyltransferases. Nat. Genet., 1998, 19(3), 219-220.
12. Yoder, J.A.; Bestor, T.H. A candidate mammalian DNA methyltransferase related to pmt1p of fission yeast. Hum. Mol. Genet., 1998, 7(2), 279-284.
13. Bestor, T.H. The DNA methyltransferases of mammals. Hum. Mol. Genet., 2000, 9(16), 2395-2402.
14. Amato, R.J. Inhibition of DNA methylation by antisense oligonucleotide MG98 as cancer therapy. Clin. Genitourin. Cancer, 2007, 5(7), 422-426.
15. Brueckner, B,; Garcia Boy, R.; Siedlecki, P.; Musch, T.; Kliem, H.C.; Zielenkiewicz, P.; Suhai, S.; Wiessler, M.; Lyko, F. Epigenetic reactivation of tumor suppressor genes by a novel smallmolecule inhibitor of human DNA methyltransferases. Cancer Res., 2005, 65(14), 6305-6311.
16. 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.; Baylin, S.B. Isolation and characterization of the cDNA encoding human DNA methyltransferase. Nucleic Acids Res., 1992, 20(9), 2287-2291.
17. Ramchandani, S.; Bigey, P.; Szyf, M. Genomic structure of the human DNA methyltransferase gene. Biol. Chem., 1998, 379(4-5), 535-540.
18. Leonhardt, H.; Bestor, TH. Structure, function and regulation of mammalian DNA methyltransferase. EXS, 1993, 64, 109-119.
19. Deng, J.; Szyf, M. Multiple isoforms of DNA methyltransferase are encoded by the vertebrate cytosine DNA methyltransferase gene. J. Biol. Chem., 1998, 273(36), 22869-22872.
20. Mertineit, C.; Yoder, J.A.; Taketo, T.; Laird, D.W.; Trasler, J.M.; Bestor, T.H. Sex-specific exons control DNA methyltransferase in mammalian germ cells. Development, 1998, 125(5), 889-897.
21. Aguirre-Arteta, A.M.; Grunewald, I.; Cardoso, M.C.; Leonhardt, H. Expression of an alternative Dnmt1 isoform during muscle differentiation. Cell Growth Differ., 2000, 11(10), 551-559.
22. Hsu, D.W.; Lin, M.J.; Lee, T.L.; Wen, S.C.; Chen, X.; Shen, C.K. Two major forms of DNA (cytosine-5) methyltransferase in human somatic tissues. Proc. Natl. Acad. Sci., 1999, 96(17), 9751-9756.
23. Bonfils, C.; Beaulieu, N.; Chan, E.; Cotton-Montpetit, J.; MacLeod, A.R. Characterization of the human DNA methyltransferase splice variant Dnmt1b. J. Biol. Chem., 2000, 275(15), 10754-10760.
24. Lin, M.J.; Lee, T.L.; Hsu, D.W.; Shen, C.K. One-codon alternative splicing of the CpG MTase Dnmt1 transcript in mouse somatic cells. FEBS Lett., 2000, 469(1), 101-104.
25. Jeltsch, A. Beyond Watson and Crick: DNA methylation and molecular enzymology of DNA methyltransferases. Chembiochem, 2000, 3(4), 274-293.
26. Kumar, S.; Cheng, X.; Klimasauskas, S.; Mi, S.; Posfai, J.; Roberts, R.J.; Wilson, G.G. The DNA (cytosine-5) methyltransferases. Nucleic Acids Res., 1994, 22(1), 1-10.
27. Malone, T.; Blumenthal, R.M.; Cheng, X. Structure-guided analysis reveals nine sequence motifs conserved among DNA aminomethyltransferases, and suggests a catalytic mechanism for these enzymes. J. Mol. Biol., 1995, 253(4), 618-632.
28. Leonhardt, H.; Page, A.W.; Weier, H.U.; Bestor, T.H. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell, 1992, 71(5), 865-873.
29. Chuang, L.S.; Ian, H.I.; Koh, T.W.; Ng, H.H.; Xu, G.; Li, B.F. Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science, 1997, 277(5334), 1996-2000.
30. Bestor, T.H.; Verdine, G.L. DNA methyltransferases. Curr. Opin. Cell. Biol., 1994, 6, 3803-3809.
31. Liu, Y.; Oakeley, E.J.; Sun, L.; Jost, J.P. Multiple domains are involved in the targeting of the mouse DNA methyltransferase to the DNA replication foci. Nucleic Acids Res., 1998, 26(4), 1038-1045.
32. Callebaut, I.; Courvalin, J.C.; Mornon, J.P. The BAH (bromoadjacent homology) domain: A link between DNA methylation, replication and transcriptional regulation. FEBS Lett., 1999, 446(1), 189-1893.
33. Chuang, L.S.; Ng, H.H.; Chia, J.N.; Li, B.F. Characterisation of independent DNA and multiple Zn-binding domains at the N terminus of human DNA-(cytosine-5) methyltransferase: Modulating the property of a DNA-binding domain by contiguous Zn-binding motifs. J. Mol. Biol., 1996, 257(5), 935-948.
34. Rountree, M.R.; Bachman, K.E.; Baylin, S.B. DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nat. Genet., 2000, 25(3), 269-277.
35. Robertson, K.D.; Ait-Si-Ali, S.; Yokochi, T.; Wade, P.A.; Jones, P.L.; Wolffe, A.P. DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nat. Genet., 2000, 25(3), 338-342.
36. Pradhan, S.; Kim, G.D. The retinoblastoma gene product interacts with maintenance human DNA (cytosine-5) methyltransferase and modulates its activity. EMBO J., 2002, 21(4), 779-788.
37. Tatematsu, K.I.; Yamazaki, T.; Ishikawa, F. MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase. Genes Cells., 2000, 5(8), 677-688.
38. Kimura, H.; Shiota, K. Methyl-CpG-binding protein, MeCP2, is a target molecule for maintenance DNA methyltransferase, Dnmt1. J. Biol. Chem., 2003, 278(7), 4806-48012.
39. Fuks, F.; Burgers, W.A.; Brehm, A.; Hughes-Davies, L.; Kouzarides, T. DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat. Genet., 2000, 24(1), 88-91.
40. Fuks, F.; Hurd, P.J.; Deplus, R.; Kouzarides, T. The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res., 2003, 31(9), 2305-2312.
41. Aapola, U.; Kawasaki, K.; Scott, H.S.; Ollila, J.; Vihinen, M.; Heino, M.; Shintani, A.; Kawasaki, K.; Minoshima, S.; Krohn, K.; Antonarakis, S.E.; Shimizu, N.; Kudoh, J.; Peterson, P. Isolation and initial characterization of a novel zinc finger gene, DNMT3L, on 21q22.3, related to the cytosine-5- methyltransferase 3 gene family. Genomics, 2000, 65(3), 293-298.
42. Xie, S.; Wang, Z.; Okano, M.; Nogami, M.; Li, Y.; He, W.W.; Okumura, K.; Li, E. Cloning, expression and chromosome locations of the human DNMT3 gene family. Gene, 1999, 236(1), 87-95.
43. Okano, M.; Takebayashi, S.; Okumura, K.; Li, E. Assignment of cytosine-5 DNA methyltransferases Dnmt3a and Dnmt3b to mouse chromosome bands 12A2-A3 and 2H1 by in situ hybridization. Cytogenet. Cell Genet., 1999, 86(3-4), 333-334.
44. Robertson, K.D.; Uzvolgyi, E.; Liang, G.; Talmadge, C.; Sumegi, J.; Gonzales, F.A.; Jones, P.A. The human DNA methyltransferases (DNMTs) 1, 3a and 3b: Coordinate mRNA expression in normal tissues and overexpression in tumors. Nucleic Acids Res., 1999, 27(11), 2291-2298.
45. Weisenberger, D.J.; Velicescu, M.; Preciado-Lopez, M.A.; Gonzales, F.A.; Tsai, Y.C.; Liang, G.; Jones, P.A. Identification and characterization of alternatively spliced variants of DNA methyltransferase 3a in mammalian cells. Gene, 2002, 298(1), 91-9.
46. Chen, T.; Ueda, Y.; Xie, S.; Li, E. A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation. J. Biol. Chem., 2002, 277(41), 38746-38754.
47. Weisenberger, D.J.; Velicescu, M.; Cheng, J.C.; Gonzales, F.A.; Liang, G.; Jones, P.A. Role of the DNA methyltransferase variant DNMT3b3 in DNA methylation. Mol. Cancer Res., 2004, 2(1), 62-72.
48. Goll, M.G.; Bestor, T.H. Eukaryotic cytosine methyltransferases. Annu. Rev. Biochem., 2005, 74, 481-514.
49. Jia, D.; Jurkowska, R.Z.; Zhang, X.; Jeltsch, A.; Cheng, X. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature, 2007, 449(7159), 248-251.
50. Cheng, X.; Blumenthal, R.M. Mammalian DNA methyltransferases: A structural perspective. Structure, 2008, 16(3), 341-350.
51. Burgers, W.A.; Fuks, F.; Kouzarides, T. DNA methyltransferases get connected to chromatin. Trends Genet., 2002, 18(6), 275-277.
52. Fuks, F.; Burgers, W.A.; Godin, N.; Kasai, M.; Kouzarides, T. Dnmt3a binds deacetylases and is recruited by a sequence-specific repressor to silence transcription. EMBO J., 2001, 20(10), 2536-2544.
53. Bachman, K.E.; Rountree, M.R.; Baylin, S.B. Dnmt3a and Dnmt3b are transcriptional repressors that exhibit unique localization properties to heterochromatin. J. Biol. Chem., 2001, 276(34), 32282-32287.
54. Lehnertz, B.; Ueda, Y.; Derijck, A.A.; Braunschweig, U.; Perez- Burgos, L.; Kubicek, S.; Chen, T.; Li, E.; Jenuwein, T.; Peters, A.H. Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr. Biol., 2003, 13(14), 1192-1200.
55. Brenner, C.; Deplus, R.; Didelot, C.; Loriot, A.; Viré, E.; De Smet, C.; Gutierrez, A.; Danovi, D.; Bernard, D.; Boon, T.; Pelicci, P.G.; Amati, B.; Kouzarides, T.; de Launoit, Y.; Di Croce, L.; Fuks, F. Myc represses transcription through recruitment of DNA methyltransferase corepressor. EMBO J. , 2005, 24(2), 336-346.
56. Qiu, C.; Sawada, K.; Zhang, X.; Cheng, X. The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds. Nat. Struct. Biol., 2002, 9(3), 217-224.
57. Stec, I.; Nagl, S.B.; van Ommen, G.J.; den Dunnen, J.T. The PWWP domain: A potential protein-protein interaction domain in nuclear proteins influencing differentiation? FEBS. Lett., 2000, 473(1), 1-5.
58. Shirohzu, H.; Kubota, T.; Kumazawa, A.; Sado, T.; Chijiwa, T.; Inagaki, K.; Suetake, I.; Tajima, S.; Wakui, K.; Miki, Y.; Hayashi, M.; Fukushima, Y.; Sasaki, H. Three novel DNMT3B mutations in Japanese patients with ICF syndrome. Am. J. Med. Genet., 2002, 112(1), 31-37.
59. Chen, T.; Tsujimoto, N.; Li, E. The PWWP domain of Dnmt3a and Dnmt3b is required for directing DNA methylation to the major satellite repeats at pericentric heterochromatin. Mol. Cell. Biol., 2004, 24(20), 9048-9058.
60. Ge, Y.Z.; Pu, M.T.; Gowher, H.; Wu, H.P.; Ding, J.P.; Jeltsch, A.; Xu, G.L. Chromatin targeting of de novo DNA methyltransferases by the PWWP domain. J. Biol. Chem., 2004, 279(24), 25447-25454.
61. Lukasik, S.M.; Cierpicki, T.; Borloz, M.; Grembecka, J.; Everett, A.; Bushweller, J.H. High resolution structure of the HDGF PWWP domain: A potential DNA binding domain. Protein Sci., 2006, 15(2), 314-23.
62. Li, B.; Zhou, J.; Liu, P.; Hu, J.; Jin, H.; Shimono, Y.; Takahashi, M.; Xu, G. Polycomb protein Cbx4 promotes SUMO modification of de novo DNA methyltransferase Dnmt3a. Biochem. J., 2007, 405(2), 369-378.
63. Kang, E.S.; Park, C.W.; Chung, J.H. Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its Nterminal region and is subject to modification by SUMO-1. Biochem. Biophys. Res. Commun., 2001, 289(4), 862-868.
64. Ling, Y.; Sankpal, U.T.; Robertson, A.K.; McNally, J.G.; Karpova, T.; Robertson, K.D. Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription. Nucleic Acids Res., 2004, 32(2), 598-610.
65. Aapola, U.; Lyle, R.; Krohn, K.; Antonarakis, S.E.; Peterson, P. Isolation and initial characterization of the mouse Dnmt3l gene. Cytogenet. Cell. Genet., 2001, 92(1-2), 122-126.
66. El-Maarri, O.; Kareta, M.S.; Mikeska, T.; Becker, T.; Diaz-Lacava, A.; Junen, J.; Nüsgen, N.; Behne, F.; Wienker, T.; Waha, A.; Oldenburg, J.; Chédin, F. A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation. Hum. Mol. Genet., 2009, 18(10), 1755-1768.
67. Bourc'his, D.; Xu, G.L.; Lin, C.S.; Bollman, B.; Bestor, T.H. Dnmt3L and the establishment of maternal genomic imprints. Science, 2001, 294(5551), 2536-2539.
68. Ooi, S.K.; Qiu, C.; Bernstein, E.; Li, K.; Jia, D.; Yang, Z.; Erdjument-Bromage, H.; Tempst, P.; Lin, S.P.; Allis, C.D.; Cheng, X.; Bestor, T.H. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature, 2007, 448(7154), 714-717. (Pubitemid 47236857)
69. Chedin, F.; Lieber, M.R.; Hsieh, C.L. The DNA methyltransferaselike protein DNMT3L stimulates de novo methylation by Dnmt3a. Proc. Natl. Acad. Sci., 2007, 99(26), 16916-16921.
70. Suetake, I.; Shinozaki, F.; Miyagawa, J.; Takeshima, H.; Tajima, S. DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. J. Biol. Chem., 2004, 279(26), 27816-27823.
71. Chen, Z.X.; Mann, J.R.; Hsieh, C.L.; Riggs, A.D.; Chédin, F. Physical and functional interactions between the human DNMT3L protein and members of the de novo methyltransferase family. J. Cell Biochem., 2005, 95(5), 902-917.
72. Aapola, U.; Liiv, I.; Peterson, P. Imprinting regulator DNMT3L is a transcriptional repressor associated with histone deacetylase activity. Nucleic Acids Res., 2002, 30(16), 3602-3608.
73. Deplus, R.; Brenner, C.; Burgers, W.A.; Putmans, P.; Kouzarides, T.; de Launoit, Y.; Fuks, F. Dnmt3L is a transcriptional repressor that recruits histone deacetylase. Nucleic Acids Res., 2002, 30(17), 3831-3838.
74. Hermann, A.; Schmitt, S.; Jeltsch, A. The human Dnmt2 has residual DNA-(cytosine-C5) methyltransferase activity. J. Biol. Chem., 2003, 278(34), 31717-31721.
75. Rai, K.; Chidester, S.; Zavala, C.V.; Manos, E.J.; James, S.R.; Karpf, A.R.; Jones, D.A.; Cairns, B.R. Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebra fish. Genes Dev., 2007, 21(3), 261-266.
76. Goll, M.G.; Kirpekar, F.; Maggert, K.A.; Yoder, J.A.;, Hsieh, C.L.; Zhang, X.; Golic, K.G.; Jacobsen, S.E.; Bestor, T.H. Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science, 2006, 311(5759), 395-398.
77. Jurkowski, T.P.; Meusburger, M.; Phalke, S.; Helm, M.; Nellen, W.; Reuter, G.; Jeltsch, A. Human DNMT2 methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalytic mechanism. RNA, 2008, 14(8), 1663-1670.
78. Ayala, T.; Rama, S.T.; Ricarda, G.; Mark, H.; and Serge, A. A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity. PLoS. Pathog., 2010, 6(2), e1000775.
79. Kunert, N.; Marhold, J.; Stanke, J.; Stach, D.; Lyko, F. A Dnmt2- like protein mediates DNA methylation in Drosophila. Development, 2003, 130(21), 5083-5090.
80. Rai, K.; Chidester, S.; Zavala, C.V.; Manos, E.J.; James, S.R.; Karpf, A.R.; Jones, D.A.; Cairns, B.R. Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish. Genes Dev., 2007, 21(3), 261-266.
81. Arturo, G.; Ralf, J.S. Evolution of dnmt-2 and mbd-2-like genes in the free-living nematodes Pristionchus pacificus, Caenorhabditis elegans and Caenorhabditis briggsae. Nucleic Acids Res., 2004, 32(21), 6388-6396.
82. Schaefer, M.; Steringer, J.P.; Lyko, F. The Drosophila Cytosine-5 Methyltransferase Dnmt2 Is Associated with the Nuclear Matrix and Can Access DNA during Mitosis. PLoS ONE, 2008, 3(1), e1414.
83. Phalke, S.; Nickel, O.; Walluscheck, D.; Hortig, F.; Onorati, M.C.; Reuter, G. Retrotransposon silencing and telomere integrity in somatic cells of Drosophila depends on the cytosine-5 methyltransferase DNMT2. Nat. Genet., 2009, 41(6), 696-702.
84. Okano, M.; Xie, S.; Li, E. Dnmt2 is not required for de novo and maintenance methylation of viral DNA in embryonic stem cells. Nucleic Acids Res., 1998, 26(11), 2536-2540.
85. Dong, A.; Yoder, J.A.; Zhang, X.; Zhou, L.; Bestor, T.H.; Cheng, X. Structure of human DNMT2, an enigmatic DNA methyltransferase homolog that displays denaturant-resistant binding to DNA. Nucleic Acids Res., 2001, 29(2), 439-448.
86. Lee, Y.F.; Tawfik, D.S.; Griffiths, A.D. Investigating the target recognition of DNA cytosine-5 methyltransferase HhaI by library selection using in vitro compartmentalisation. Nucleic. Acids. Res., 2002, 30(22), 4937-4944.
87. Schaefer, M.; Lyko, F. Solving the Dnmt2 enigma. Chromosoma, 2010, 119, 35-40.
88. Reither, S.; Li, F.; Gowher, H.; Jeltsch, A. Catalytic mechanism of DNA-(cytosine-C5)-methyltransferases revisited: Covalent intermediate formation is not essential for methyl group transfer by the murine Dnmt3a enzyme. J. Mol. Biol., 2003, 329(4), 675-684.
89. Klimasauskas, S.; Roberts, R.J. M.HhaI binds tightly to substrates containing mismatches at the target base. Nucleic Acids Res., 1995, 23(8), 1388-1395.
90. Jeltsch, A. The cytosine N4-methyltransferase M.PvuII also modifies adenine residues. Biol. Chem., 2001, 382(4), 707-710.
91. Klimasauskas, S.; Kumar, S.; Roberts, R.J.; Cheng, X. HhaI methyltransferase flips its target base out of the DNA helix. Cell, 1994, 76(2), 357-369. (Pubitemid 24046697)
92. Reinisch, K.M.; Chen, L.; Verdine, G.L.; Lipscomb, W.N. The crystal structure of HaeIII methyltransferase convalently complexed to DNA: An extrahelical cytosine and rearranged base pairing. Cell, 1995, 82(1), 143-153.
93. O'Gara, M.; Horton, J.R.; Roberts, R.J.; Cheng, X. Structures of HhaI methyltransferase complexed with substrates containing mismatches at the target base. Nat. Struct. Biol., 1998, 5(10), 872-877.
94. Roberts, R.J.; Cheng, X. Base flipping. Annu. Rev. Biochem., 1998, 67, 181-198.
95. Parikh, S.S.; Mol, C.D.; Slupphaug, G.; Bharati, S.; Krokan, H.E.; Tainer, J.A. Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA. EMBO J., 1998, 17, 5214-5226.
96. Barrett, T.E.; Scharer, O.D.; Savva, R.; Brown, T.; Jiricny, J.; Verdine, G.L.; Pearl, L.H. Crystal structure of a thwarted mismatch glycosylase DNA repair complex. EMBO. J., 1999, 18, 6599-6609.
97. Cheng, X.; Blumenthal, R.M. Finding a basis for flipping bases. Structure, 1996, 4(6), 639-645.
98. Mi, S.; Alonso, D.; Roberts, R.J. Functional analysis of Gln-237 mutants of HhaI methyltransferase. Nucleic Acids Res., 1995, 23(4), 620-627.
99. Estabrook, R.A.; Lipson, R.; Hopkins, B.; Reich, N. The coupling of tight DNA binding and base flipping: Identification of a conserved structural motif in base flipping enzymes. J. Biol. Chem., 2004, 279(30), 31419-31428.
100. Shieh, F.K.; Youngblood, B.; Reich, N.O. The role of Arg165 towards base flipping, base stabilization and catalysis in M.HhaI. J. Mol. Biol., 2006, 362(3), 516-527.
101. Vilkaitis, G.; Dong, A.; Weinhold, E.; Cheng, X.; Klimasauskas, S. Functional roles of the conserved threonine 250 in the target recognition domain of HhaI DNA methyltransferase. J. Biol. Chem., 2000, 275(49), 38722-38730.
102. Estabrook, R.A.; Reich, N. Observing an induced-fit mechanism during sequence-specific DNA methylation. J. Biol. Chem., 2006, 281(48), 37205-37214.
103. Svedruzić, Z.M. Mammalian cytosine DNA methyltransferase Dnmt1: Enzymatic mechanism, novel mechanism-based inhibitors, and RNA-directed DNA methylation. Curr. Med. Chem., 2008, 15(1), 92-106.
104. Bostick, M.; Kim, J.K.; Estéve, P.O.; Clark, A.; Pradhan, S.; Jacobsen, S.E. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science, 2007, 317(5845), 1760-1764.
105. Sharif, J.; Muto, M.; Takebayashi, S.; Suetake, I.; Iwamatsu, A.; Endo, T.A.; Shinga, J.; Mizutani-Koseki, Y.; Toyoda, T.; Okamura, K.; Tajima, S.; Mitsuya, K.; Okano, M.; Koseki, H. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature, 2007, 450(7171), 908-912.
106. Arita, K.; Ariyoshi, M.; Tochio, H.; Nakamura, Y.; Shirakawa, M. Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism. Nature, 2008, 455(7214), 818-821.
107. Avvakumov, G.V.; Walker, J.R.; Xue, S.; Li, Y.; Duan, S.; Bronner, C.; Arrowsmith, C.H.; Dhe-Paganon, S. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature, 2008, 455(7214), 822-825.
108. Hashimoto, H.; Horton, J.R.; Zhang, X.; Bostick, M.; Jacobsen, S.E.; Cheng, X. The SRA domain of UHRF1 flips 5- methylcytosine out of the DNA helix. Nature, 2008, 455(7214), 826-829.
109. Roth, M.; Helm-Kruse, S.; Friedrich, T.; Jeltsch, A. Functional roles of conserved amino acid residues in DNA methyltransferases investigated by site-directed mutagenesis of the EcoRV adenine- N6-methyltransferase. J. Biol. Chem., 1998, 273(28), 17333-17342.
110. Tran, P.H.; Korszun, Z.R.; Cerritelli, S.; Springhorn, S.S.; Lacks, S.A. Crystal structure of the DpnM DNA adenine methyltransferase from the DpnII restriction system of streptococcus pneumoniae bound to S-adenosylmethionine. Structure, 1998, 6(12), 1563-1575.
111. O'Gara, M.; Zhang, X.; Roberts, R.J.; Cheng, X. Structure of a binary complex of HhaI methyltransferase with S-adenosyl-Lmethionine formed in the presence of a short non-specific DNA oligonucleotide. J. Mol. Biol., 1999, 287(2), 201-209.
112. Schluckebier, G.; Kozak, M.; Bleimling, N.; Weinhold, E.; Saenger, W. Differential binding of S-adenosylmethionine Sadenosylhomocysteine and Sinefungin to the adenine-specific DNA methyltransferase M.TaqI. J. Mol. Biol., 1997, 265(1), 56-67.
113. Chen, L.; MacMillan, A.M.; Chang, W.; Ezaz-Nikpay, K.; Lane, W.S.; Verdine, G.L. Direct identification of the active-site nucleophile in a DNA (cytosine-5)-methyltransferase. Biochemistry, 1991, 30(46), 11018-11025.
114. Wyszynski, M.W.; Gabbara, S.; Kubareva, E.A.; Romanova, E.A.; Oretskaya, T.S.; Gromova, E.S.; Shabarova, Z.A.; Bhagwat, A.S. The cysteine conserved among DNA cytosine methylases is required for methyl transfer, but not for specific DNA binding. Nucleic. Acids. Res., 1993, 21(2), 295-301.
115. O'Gara, M.; Klimasauskas, S.; Roberts, R.J.; Cheng, X. Enzymatic C5-cytosine methylation of DNA: Mechanistic implications of new crystal structures for HhaL methyltransferase-DNA-AdoHcy complexes. J. Mol. Biol., 1996, 261(5), 634-645.
116. Zhang, X.; Bruice, T.C. The mechanism of M.HhaI DNA C5 cytosine methyltransferase enzyme: A quantum mechanics/molecular mechanics approach. Proc. Natl. Acad. Sci., 2006, 103(16), 6148-6153.
117. Stresemann, C.; Lyko, F. Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine. Int. J. Cancer, 2008, 123(1), 8-13.
118. Youngblood, B.; Shieh, F.K.; Buller, F.; Bullock, T.; Reich, N.O. S-adenosyl-L-methionine-dependent methyl transfer: Observable precatalytic intermediates during DNA cytosine methylation. Biochemistry, 2007, 46(30), 8766-8775.
119. Shieh, F.K.; Youngblood, B.; Reich, N.O. The role of Arg165 towards base flipping, base stabilization and catalysis in M.HhaI. J. Mol. Biol., 2006, 362(3), 516-527.
120. Gabbara, S.; Sheluho, D.; Bhagwat, A.S. Cytosine methyltransferase from Escherichia coli in which active site cysteine is replaced with serine is partially active. Biochemistry, 1995, 34(27), 8914-8923.
121. Lau, E.Y.; Bruice, T.C. Active site dynamics of the HhaI methyltransferase: Insights from computer simulation. J. Mol. Biol., 1999, 293(1), 9-18.
122. Shen, J.C.; Rideout, W.M.; Jones, P.A. High frequency mutagenesis by a DNA methyltransferase. Cell, 1992, 71(7), 1073-1080.
123. Zingg, J.M.; Shen, J.C.; Jones, P.A. Enzyme-mediated cytosine deamination by the bacterial methyltransferase M.MspI. Biochem. J., 1998, 332, 223-230.
124. Sharath, A.N.; Weinhold, E.; Bhagwat, A.S. Reviving a dead enzyme: Cytosine deaminations promoted by an inactive DNA methyltransferase and an S-adenosylmethionine analogue. Biochemistry, 2000, 39(47), 14611-14616.
125. Svedruzić, Z.M.; Reich, N.O. The mechanism of target base attack in DNA cytosine carbon 5 methylation. Biochemistry, 2004, 43(36), 11460-11473.
126. Svedruzić, Z.M.; Reich, N.O. DNA cytosine C5 methyltransferase Dnmt1: Catalysis-dependent release of allosteric inhibition. Biochemistry, 2005, 44(27), 9472-9485
127. Reither, S.; Li, F.; Gowher, H.; Jeltsch, A. Catalytic mechanism of DNA-(cytosine-C5)-methyltransferases revisited: Covalent intermediate formation is not essential for methyl group transfer by the murine Dnmt3a enzyme. J. Mol. Biol., 2003, 329(4), 675-684.
128. Gruenbaum, Y.; Cedar, H.; Razin, A. Substrate and sequence specificity of a eukaryotic DNA methylase. Nature, 1982, 295(5850), 620-622.
129. Lin, X.; Asgari, K.; Putzi, M.J.; Gage, W.R.; Yu, X.; Cornblatt, B.S.; Kumar, A.; Piantadosi, S.; DeWeese, T.L.; De Marzo, A.M.; Nelson, W.G. Reversal of GSTP1 CpG island hypermethylation and reactivation of pi-class glutathione S-transferase (GSTP1) expression in human prostate cancer cells by treatment with procainamide. Cancer Res., 2001, 61(24), 8611-8616.
130. Lee, B.H.; Yegnasubramanian, S.; Lin, X.; Nelson, W.G. Procainamide is a specific inhibitor of DNA methyltransferase 1. J. Biol. Chem., 2005, 280(49), 40749-40756.
131. Bolden, A.; Ward, C.; Siedlecki, J.A.; Weissbach, A. DNA methylation. Inhibition of de novo and maintenance methylation in vitro by RNA and synthetic polynucleotides. J. Biol. Chem., 1984, 259(20), 12437-12443.
132. Flynn, J.; Glickman, J.F.; Reich, N.O. Murine DNA cytosine-C5 methyltransferase: Pre-steady- and steady-state kinetic analysis with regulatory DNA sequences. Biochemistry, 1996, 35(23), 7308-7315.
133. Flynn, J.; Azzam, R.; Reich, N. DNA binding discrimination of the murine DNA cytosine-C5 methyltransferase. J. Mol. Biol., 1998, 279(1), 101-116.
134. Achour, M.; Jacq, X.; Rondé, P.; Alhosin, M.; Charlot, C.; Chataigneau, T.; Jeanblanc, M.; Macaluso, M.; Giordano, A.; Hughes, A.D.; Schini-Kerth, V.B.; Bronner, C. The interaction of the SRA domain of ICBP90 with a novel domain of DNMT1 is involved in the regulation of VEGF gene expression. Oncogene, 2008, 27, 2187-2197.
135. Unoki, M.; Brunet, J.; Mousli, M. Drug discovery targeting epigenetic codes: The great potential of UHRF1, which links DNA methylation and histone modifications, as a drug target in cancers and toxoplasmosis. Biochem. Pharmacol., 2009, 78(10), 1279-1288.
136. Flynn, J.; Fang, J.Y.; Mikovits, J.A.; Reich, N.O. A potent cellactive allosteric inhibitor of murine DNA cytosine C5 methyltransferase. J. Biol. Chem., 2003, 278(10), 8238-8243.
137. Bacolla, A.; Pradhan, S.; Roberts, R.J.; Wells, R.D. Recombinant human DNA (cytosine-5) methyltransferase. II. Steady-state kinetics reveal allosteric activation by methylated dna. J. Biol. Chem., 1999, 274(46), 33011-33019.
138. Goyal, R.; Reinhardt, R.; Jeltsch, A. Accuracy of DNA methylation pattern preservation by the Dnmt1 methyltransferase. Nucleic. Acids. Res., 2006, 34(4), 1182-1188.
139. Zaratiegui, M.; Irvine, D.V.; Martienssen, R.A. Noncoding RNAs and gene silencing. Cell, 2007, 128(4), 763-76.
140. Biniszkiewicz, D.; Gribnau, J.; Ramsahoye, B.; Gaudet, F.; Eggan, K.; Humpherys, D.; Mastrangelo, M.A.; Jun, Z.; Walter, J.; Jaenisch, R. Dnmt1 overexpression causes genomic hypermethylation, loss of imprinting, and embryonic lethality. Mol. Cell. Biol., 2002, 22(7), 2124-2135.
141. Datta, J.; Ghoshal, K.; Sharma, S.M.; Tajima, S.; Jacob, S.T. Biochemical fractionation reveals association of DNA methyltransferase (Dnmt) 3b with Dnmt1 and that of Dnmt 3a with a histone H3 methyltransferase and Hdac1. J. Cell. Biochem., 2003, 88(5), 855-864.
142. Bourc'his, D.; Xu, G.L.; Lin, C.S.; Bollman, B.; Bestor, T.H. Dnmt3L and the establishment of maternal genomic imprints. Science, 2001, 294(5551), 2536-2539.
143. Kaneda, M.; Okano, M.; Hata, K.; Sado, T.; Tsujimoto, N.; Li, E.; Sasaki, H. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature, 2004, 429(6994), 900-903.
144. Gowher, H.; Jeltsch, A. Molecular enzymology of the catalytic domains of the Dnmt3a and Dnmt3b DNA methyltransferases. J. Biol. Chem., 2002, 277(23), 20409-20414. (Pubitemid 34967336)
145. Ramsahoye, B.H.; Biniszkiewicz, D.; Lyko, F.; Clark, V.; Bird, A.P.; Jaenisch, R. Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc. Natl. Acad. Sci., 2000, 97(10), 5237-5242.
146. Dodge, J.E.; Ramsahoye, B.H.; Wo, Z.G.; Okano, M.; Li, E. De novo methylation of MMLV provirus in embryonic stem cells: CpG versus non-CpG methylation. Gene, 2002, 289(1-2), 41-48.
147. Cedar, H.; Bergman, Y. Linking DNA methylation and histone modification: Patterns and paradigms. Nat. Rev. Genet., 2009, 10(5), 295-304.
148. Lin, I.G.; Han, L.; Taghva, A.; O'Brien, L.E.; Hsieh, C.L. Murine de novo methyltransferase Dnmt3a demonstrates strand asymmetry and site preference in the methylation of DNA in vitro. Mol. Cell. Biol., 2002, 22(3), 704-723.
149. Handa. V.; Jeltsch, A. Profound flanking sequence preference of Dnmt3a and Dnmt3b mammalian DNA methyltransferases shape the human epigenome. J. Mol. Biol., 2005, 348(5), 1103-1012.
150. Hermann, A.; Goyal, R.; Jeltsch, A. The Dnmt1 DNA-(cytosine- C5)-methyltransferase methylates DNA processively with high preference for hemimethylated target sites. J. Biol. Chem., 2004, 279(46), 48350-48359.
151. Liang, G.; Chan, M.F.; Tomigahara, Y.; Tsai, Y.C.; Gonzales, F.A.; Li, E.; Laird, P.W.; Jones, P.A. Cooperativity between DNA methyltransferases in the maintenance methylation of repetitive elements. Mol. Cell. Biol., 2002, 22(2), 480-491.
152. Chen, T.; Ueda, Y.; Dodge, J.E.; Wang, Z.; Li, E. Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b. Mol. Cell. Biol., 2003, 23(16), 5594-5605.