Targeted methylation and gene silencing of VEGF-A in human cells by using a designed Dnmt3a-Dnmt3L single-chain fusion protein with increased DNA methylation activity

Journal of Molecular Biology

Volumn 425, Issue 3, 2013, Pages 479-491

  Siddique, Abu Nasar ^a   Nunna, Suneetha ^a,b   Rajavelu, Arumugam ^a,b   Zhang, Yingying ^a   Jurkowska, Renata Z ^a,b   Reinhardt, Richard ^c   Rots, Marianne G ^d   Ragozin, Sergey ^a,b   Jurkowski, Tomasz P ^a,b   Jeltsch, Albert ^a,b  

^a JACOBS UNIVERSITY BREMEN   (Germany)

^b UNIVERSITY OF STUTTGART   (Germany)

^c Max Planck Genomzentrum Köln   (Germany)

^d UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

Author keywords

DNA methyltransferase; gene regulation; Keywords; protein design; protein DNA interaction; zinc finger domain

Indexed keywords

AMINO ACID; DNA METHYLTRANSFERASE 3A; HETERODIMER; HYBRID PROTEIN; VASCULOTROPIN A; ZINC FINGER PROTEIN;

ARTICLE; BACTERIAL CELL; CATALYSIS; CHIMERA; CONTROLLED STUDY; CPG ISLAND; CRYSTAL STRUCTURE; DNA METHYLATION; DOWN REGULATION; ENZYME STRUCTURE; ESCHERICHIA COLI; GENE SILENCING; GENETIC VARIABILITY; HUMAN; HUMAN CELL; IN VITRO STUDY; MOLECULAR DYNAMICS; MOLECULAR MIMICRY; MOLECULARLY TARGETED THERAPY; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN PURIFICATION;

BACTERIA (MICROORGANISMS);

EID: 84872865881     PISSN: 00222836     EISSN: 10898638     Source Type: Journal    
DOI: 10.1016/j.jmb.2012.11.038     Document Type: Article

References (67)

1. R.J. Klose, and A.P. Bird Genomic DNA methylation: the mark and its mediators Trends Biochem. Sci. 31 2006 89 97
2. R.Z. Jurkowska, T.P. Jurkowski, and A. Jeltsch Structure and function of mammalian DNA methyltransferases ChemBioChem 12 2011 206 222
3. J.A. Law, and S.E. Jacobsen Establishing, maintaining and modifying DNA methylation patterns in plants and animals Nat. Rev. Genet. 11 2010 204 220
4. S. Feng, S.E. Jacobsen, and W. Reik Epigenetic reprogramming in plant and animal development Science 330 2010 622 627
5. H. Gowher, and A. Jeltsch Molecular enzymology of the catalytic domains of the Dnmt3a and Dnmt3b DNA methyltransferases J. Biol. Chem. 277 2002 20409 20414
6. D. Bourc'his, G.L. Xu, C.S. Lin, B. Bollman, and T.H. Bestor Dnmt3L and the establishment of maternal genomic imprints Science 294 2001 2536 2539
7. K. Hata, M. Okano, H. Lei, and E. Li Dnmt3L cooperates with the Dnmt3 family of de novo DNA methyltransferases to establish maternal imprints in mice Development 129 2002 1983 1993
8. H. Gowher, K. Liebert, A. Hermann, G. Xu, and A. Jeltsch Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)- methyltransferases by Dnmt3L J. Biol. Chem. 280 2005 13341 13348
9. D. Jia, R.Z. Jurkowska, X. Zhang, A. Jeltsch, and X. Cheng Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation Nature 449 2007 248 251
10. F. Chedin, M.R. Lieber, and C.L. Hsieh The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a Proc. Natl Acad. Sci. USA 99 2002 16916 16921
11. Z.X. Chen, J.R. Mann, C.L. Hsieh, A.D. Riggs, and F. Chedin Physical and functional interactions between the human DNMT3L protein and members of the de novo methyltransferase family J. Cell. Biochem. 95 2005 902 917
12. I. Suetake, F. Shinozaki, J. Miyagawa, H. Takeshima, and S. Tajima DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction J. Biol. Chem. 279 2004 27816 27823
13. M.S. Kareta, Z.M. Botello, J.J. Ennis, C. Chou, and F. Chedin Reconstitution and mechanism of the stimulation of de novo methylation by human DNMT3L J. Biol. Chem. 281 2006 25893 25902
14. A. Jeltsch, R.Z. Jurkowska, T.P. Jurkowski, K. Liebert, P. Rathert, and M. Schlickenrieder Application of DNA methyltransferases in targeted DNA methylation Appl. Microbiol. Biotechnol. 75 2007 1233 1240
15. R.Z. Jurkowska, and A. Jeltsch Silencing of gene expression by targeted DNA methylation: concepts and approaches Methods Mol. Biol. 649 2010 149 161
16. M. de Groote, P.J. Verschure, and M.G. Rots Epigenetic editing: targeted rewriting of epigenetic marks to modulate expression of selected target genes Nucleic Acids Res. 40 2012 10596 10613
17. D. Carroll, J.J. Morton, K.J. Beumer, and D.J. Segal Design, construction and in vitro testing of zinc finger nucleases Nat. Protoc. 1 2006 1329 1341
18. M.S. Bhakta, and D.J. Segal The generation of zinc finger proteins by modular assembly Methods Mol. Biol. 649 2010 3 30
19. S. Alwin, M.B. Gere, E. Guhl, K. Effertz, C.F. Barbas 3rd, and D.J. Segal Custom zinc-finger nucleases for use in human cells Mol. Ther. 12 2005 610 617
20. Mackay, J. P. & Segal, D. J.; Eds. (2010). Engineered zinc finger proteins. In Methods in Molecular Biology (Walker, J. M.; ed), vol. 649, Humana Press.
21. F. Li, M. Papworth, M. Minczuk, C. Rohde, Y. Zhang, S. Ragozin, and A. Jeltsch Chimeric DNA methyltransferases target DNA methylation to specific DNA sequences and repress expression of target genes Nucleic Acids Res. 35 2007 100 112
22. A.G. Rivenbark, S. Stolzenburg, A.S. Beltran, X. Yuan, M.G. Rots, B.D. Strahl, and P. Blancafort Epigenetic reprogramming of cancer cells via targeted DNA methylation Epigenetics 7 2012 350 360
23. H.F. Dvorak Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy J. Clin. Oncol. 20 2002 4368 4380
24. S. Shinkaruk, M. Bayle, G. Lain, and G. Deleris Vascular endothelial cell growth factor (VEGF), an emerging target for cancer chemotherapy Curr. Med. Chem. Anticancer Agents 3 2003 95 117
25. A. Hoeben, B. Landuyt, M.S. Highley, H. Wildiers, A.T. Van Oosterom, and E.A. De Bruijn Vascular endothelial growth factor and angiogenesis Pharmacol. Rev. 56 2004 549 580
26. A.M. Byrne, D.J. Bouchier-Hayes, and J.H. Harmey Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF) J. Cell. Mol. Med. 9 2005 777 794
27. F.W. Studier Protein production by auto-induction in high density shaking cultures Protein Expr. Purif. 41 2005 207 234
28. R.Z. Jurkowska, N. Anspach, C. Urbanke, D. Jia, R. Reinhardt, and W. Nellen Formation of nucleoprotein filaments by mammalian DNA methyltransferase Dnmt3a in complex with regulator Dnmt3L Nucleic Acids Res. 36 2008 6656 6663
29. R.Z. Jurkowska, A. Rajavelu, N. Anspach, C. Urbanke, G. Jankevicius, and S. Ragozin Oligomerization and binding of the Dnmt3a DNA methyltransferase to parallel DNA molecules: heterochromatic localization and role of Dnmt3L J. Biol. Chem. 286 2011 24200 24207
30. R.Z. Jurkowska, A.N. Siddique, T.P. Jurkowski, and A. Jeltsch Approaches to enzyme and substrate design of the murine Dnmt3a DNA methyltransferase ChemBioChem 12 2011 1589 1594
31. I.G. Lin, L. Han, A. Taghva, L.E. O'Brien, and C.L. Hsieh Murine de novo methyltransferase Dnmt3a demonstrates strand asymmetry and site preference in the methylation of DNA in vitro Mol. Cell. Biol. 22 2002 704 723
32. V. Handa, and A. Jeltsch Profound flanking sequence preference of Dnmt3a and Dnmt3b mammalian DNA methyltransferases shape the human epigenome J. Mol. Biol. 348 2005 1103 1112
33. H. Gowher, P. Loutchanwoot, O. Vorobjeva, V. Handa, R.Z. Jurkowska, T.P. Jurkowski, and A. Jeltsch Mutational analysis of the catalytic domain of the murine Dnmt3a DNA-(cytosine C5)-methyltransferase J. Mol. Biol. 357 2006 928 941
34. B.L. Wienholz, M.S. Kareta, A.H. Moarefi, C.A. Gordon, P.A. Ginno, and F. Chedin DNMT3L modulates significant and distinct flanking sequence preference for DNA methylation by DNMT3A and DNMT3B in vivo PLoS Genet. 6 2010
35. H. Gowher, and A. Jeltsch Enzymatic properties of recombinant Dnmt3a DNA methyltransferase from mouse: the enzyme modifies DNA in a non-processive manner and also methylates non-CpG sites J. Mol. Biol. 309 2001 1201 1208
36. P.Q. Liu, E.J. Rebar, L. Zhang, Q. Liu, A.C. Jamieson, and Y. Liang Regulation of an endogenous locus using a panel of designed zinc finger proteins targeted to accessible chromatin regions. Activation of vascular endothelial growth factor A J. Biol. Chem. 276 2001 11323 11334
37. E.J. Rebar, Y. Huang, R. Hickey, A.K. Nath, D. Meoli, and S. Nath Induction of angiogenesis in a mouse model using engineered transcription factors Nat. Med. 8 2002 1427 1432
38. A.W. Snowden, L. Zhang, F. Urnov, C. Dent, Y. Jouvenot, and X. Zhong Repression of vascular endothelial growth factor A in glioblastoma cells using engineered zinc finger transcription factors Cancer Res. 63 2003 8968 8976
39. J. Yu, L. Lei, Y. Liang, L. Hinh, R.P. Hickey, and Y. Huang An engineered VEGF-Activating zinc finger protein transcription factor improves blood flow and limb salvage in advanced-Age mice FASEB J. 20 2006 479 481
40. Y. Liu, S. Figley, S.K. Spratt, G. Lee, D. Ando, R. Surosky, and M.G. Fehlings An engineered transcription factor which activates VEGF-A enhances recovery after spinal cord injury Neurobiol. Dis. 37 2010 384 393
41. E.J. Pawson, B. Duran-Jimenez, R. Surosky, H.E. Brooke, S.K. Spratt, D.R. Tomlinson, and N.J. Gardiner Engineered zinc finger protein-mediated VEGF-A activation restores deficient VEGF-A in sensory neurons in experimental diabetes Diabetes 59 2010 509 518
42. C. Rohde, Y. Zhang, R. Reinhardt, and A. Jeltsch BISMA - fast and accurate bisulfite sequencing data analysis of individual clones from unique and repetitive sequences BMC Bioinformatics 11 2010 230
43. J.S. Huston, J. McCartney, M.S. Tai, C. Mottola-Hartshorn, D. Jin, and F. Warren Medical applications of single-chain antibodies Int. Rev. Immunol. 10 1993 195 217
44. S.D. Nuttall, R.A. Irving, and P.J. Hudson Immunoglobulin VH domains and beyond: design and selection of single-domain binding and targeting reagents Curr. Pharm. Biotechnol. 1 2000 253 263
45. T.H. Hansen, J.M. Connolly, K.G. Gould, and D.H. Fremont Basic and translational applications of engineered MHC class I proteins Trends Immunol. 31 2010 363 369
46. J.A. Mullaney, and B.H. Rehm Design of a single-chain multi-enzyme fusion protein establishing the polyhydroxybutyrate biosynthesis pathway J. Biotechnol. 147 2010 31 36
47. J. Chen, S. Pongor, and A. Simoncsits Recognition of DNA by single-chain derivatives of the phage 434 repressor: high affinity binding depends on both the contacted and non-contacted base pairs Nucleic Acids Res. 25 1997 2047 2054
48. A. Simoncsits, J. Chen, P. Percipalle, S. Wang, I. Toro, and S. Pongor Single-chain repressors containing engineered DNA-binding domains of the phage 434 repressor recognize symmetric or asymmetric DNA operators J. Mol. Biol. 267 1997 118 131
49. A. Simoncsits, M.L. Tjornhammar, T. Rasko, A. Kiss, and S. Pongor Covalent joining of the subunits of a homodimeric type II restriction endonuclease: single-chain PvuII endonuclease J. Mol. Biol. 309 2001 89 97
50. T. Liang, J. Chen, M.L. Tjornhammar, S. Pongor, and A. Simoncsits Modular construction of extended DNA recognition surfaces: mutant DNA-binding domains of the 434 repressor as building blocks Protein Eng. 14 2001 591 599
51. B. Schierling, A.J. Noel, W. Wende, T. Hien le, E. Volkov, and E. Kubareva Controlling the enzymatic activity of a restriction enzyme by light Proc. Natl Acad. Sci. USA 107 2010 1361 1366
52. K. Eisenschmidt, T. Lanio, A. Simoncsits, A. Jeltsch, V. Pingoud, W. Wende, and A. Pingoud Developing a programmed restriction endonuclease for highly specific DNA cleavage Nucleic Acids Res. 33 2005 7039 7047
53. A.M. Gronenborn Protein acrobatics in pairs - dimerization via domain swapping Curr. Opin. Struct. Biol. 19 2009 39 49
54. J. Carey, S. Lindman, M. Bauer, and S. Linse Protein reconstitution and three-dimensional domain swapping: benefits and constraints of covalency Protein Sci. 16 2007 2317 2333
55. A.L. Mulkeen, T. Silva, P.S. Yoo, J.C. Schmitz, E. Uchio, E. Chu, and C. Cha Short interfering RNA-mediated gene silencing of vascular endothelial growth factor: effects on cellular proliferation in colon cancer cells Arch. Surg. 141 2006 367 374 [discussion 374]
56. M.P. Turunen, T. Lehtola, S.E. Heinonen, G.S. Assefa, P. Korpisalo, and R. Girnary Efficient regulation of VEGF expression by promoter-targeted lentiviral shRNAs based on epigenetic mechanism: a novel example of epigenetherapy Circ. Res. 105 2009 604 609
57. A.E. Smith, P.J. Hurd, A.J. Bannister, T. Kouzarides, and K.G. Ford Heritable gene repression through the action of a directed DNA methyltransferase at a chromosomal locus J. Biol. Chem. 283 2008 9878 9885
58. M. Minczuk, M.A. Papworth, P. Kolasinska, M.P. Murphy, and A. Klug Sequence-specific modification of mitochondrial DNA using a chimeric zinc finger methylase Proc. Natl. Acad. Sci. USA 103 2006 19689 19694
59. W.G. Kaelin Jr. Molecular biology. Use and abuse of RNAi to study mammalian gene function Science 337 2012 421 422
60. A.J. Bogdanove, and D.F. Voytas TAL effectors: customizable proteins for DNA targeting Science 333 2011 1843 1846
61. A. Jeltsch, and T. Lanio Site-directed mutagenesis by polymerase chain reaction Methods Mol. Biol. 182 2002 85 94
62. W.M. Gommans, P.M. McLaughlin, B.I. Lindhout, D.J. Segal, D.J. Wiegman, and H.J. Haisma Engineering zinc finger protein transcription factors to downregulate the epithelial glycoprotein-2 promoter as a novel anti-cancer treatment Mol. Carcinog. 46 2007 391 401
63. S. Stolzenburg, A. Bilsland, W.N. Keith, and M.G. Rots Modulation of gene expression using zinc finger-based artificial transcription factors Methods Mol. Biol. 649 2010 117 132
64. M. Roth, and A. Jeltsch Biotin-Avidin microplate assay for the quantitative analysis of enzymatic methylation of DNA by DNA methyltransferases Biol. Chem. 381 2000 269 272
65. K. Liebert, and A. Jeltsch Detection and quantitation of the activity of DNA methyltransferases using a biotin/avidin microplate assay Methods Mol. Biol. 418 2008 149 156
66. Y. Zhang, C. Rohde, S. Tierling, T.P. Jurkowski, C. Bock, and D. Santacruz DNA methylation analysis of chromosome 21 gene promoters at single base pair and single allele resolution PLoS Genet. 5 2009 e1000438
67. C. Rohde, Y. Zhang, T.P. Jurkowski, H. Stamerjohanns, R. Reinhardt, and A. Jeltsch Bisulfite sequencing Data Presentation and Compilation (BDPC) web server - a useful tool for DNA methylation analysis Nucleic Acids Res. 36 2008 e34