Analysis of an artificial zinc finger epigenetic modulator: Widespread binding but limited regulation

Nucleic Acids Research

Volumn 42, Issue 16, 2014, Pages 10856-10868

  Grimmer, Matthew R ^a,b   Stolzenburg, Sabine ^c,d   Ford, Ethan ^d   Lister, Ryan ^d   Blancafort, Pilar ^c,d,e   Farnham, Peggy J ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^e UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

HISTONE METHYLTRANSFERASE; TRANSCRIPTION FACTOR SOX2; ZINC FINGER PROTEIN; DNA BINDING PROTEIN; PROTEIN BINDING; TRANSCRIPTION FACTOR;

ARTICLE; BINDING SITE; CONTROLLED STUDY; DOWN REGULATION; EPIGENETICS; GENE EXPRESSION REGULATION; GENE INTERACTION; GENE REPRESSION; GENETIC VARIABILITY; HISTONE METHYLATION; MCF 7 CELL LINE; MICROCHIP ANALYSIS; NUCLEOTIDE SEQUENCE; PROMOTER REGION; PROTEIN DNA BINDING; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; REGULATORY MECHANISM; SEQUENCE ANALYSIS; SOX2 GENE; CHEMISTRY; GENETIC EPIGENESIS; HUMAN; HUMAN GENOME; METABOLISM;

BINDING SITES; DNA-BINDING PROTEINS; EPIGENESIS, GENETIC; GENOME, HUMAN; HUMANS; MCF-7 CELLS; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; TRANSCRIPTION FACTORS; ZINC FINGERS;

EID: 84913620157     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gku708     Document Type: Article

References (66)

1. Lee, T.I. and Young, R.A. Lee, T.I. and Young, R.A. (2013) Transcriptional regulation and its misregulation in disease. Cell, 152, 1237-1251.
2. Farnham, P.J.Farnham, P.J. (2009) Insights from genomic profiling of transcription factors. Nature Rev. Genet., 10, 605-616.
3. Yang, X., Lay, F., Han, H., and Jones, P.A.Yang, X., Lay, F., Han, H., and Jones, P.A. (2010) Targeting DNA methylation for epigenetic therapy. Trends Pharmacol. Sci., 31, 536-546.
4. Li, X., Zhang, J., Xie, Y., Jiang, Y., Yingjie, Z., and Xu, W.Li, X., Zhang, J., Xie, Y., Jiang, Y., Yingjie, Z., and Xu, W. (2014) Curr. Drug Targets, 15, 622-634.
5. West, A.C. and Johnstone, R.W.West, A.C. and Johnstone, R.W. (2014) New and emerging HDAC inhibitors for cancer treatment. J. Clin. Invest., 124, 30-39.
6. Lovén, J., Hoke, H.A., Lin, C.Y., Lau, A., Orlando, D.A., Vakoc, C.R., Bradner, J.E., Lee, T.I., and Young, R.A.Lovén, J., Hoke, H.A., Lin, C.Y., Lau, A., Orlando, D.A., Vakoc, C.R., Bradner, J.E., Lee, T.I., and Young, R.A. (2013) Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell, 153, 320-334.
7. Dobbelstein, M. and Moll, U.Dobbelstein, M. and Moll, U. (2014) Targeting tumour-supportive cellular machineries in anticancer drug development. Nature reviews. Drug Discov., 13, 179-196.
8. Segal, D.J. and Meckler, J.F.Segal, D.J. and Meckler, J.F. (2013) Genome engineering at the dawn of the golden age. Annu. Rev. Genomics Hum Genet., 14, 135-158
9. Grimmer, M.R. and Farnham, P.J.in pressGrimmer, M.R. and Farnham, P.J. (2014) Can genome engineering be used to target cancer-associated enhancers?. Epigenomics,.
10. Verschure, P.J., Visser, A.E., and Rots, M.G. Verschure, P.J., Visser, A.E., and Rots, M.G. (2006) Step out of the groove: epigenetic gene control systems and engineered transcription factors. Adv. Genet., 56, 163-204.
11. Liu, Q., Segal, D.J., Ghiara, J.B., and Barbas, C.F. IIILiu, Q., Segal, D.J., Ghiara, J.B., and Barbas, C.F. III (1997) Design of polydactyl zinc-finger proteins for unique addressing within complex genomes. Proc. Natl. Acad. Sci. U.S.A., 94, 5525-5530.
12. Tadepally, H., Burger, G., and Aubry, M.Tadepally, H., Burger, G., and Aubry, M. (2008) Evolution of C2H2-zinc finger genes and subfamilies in mammals: species-specific duplication and loss of clusters, genes and effector domains. BMC Evol. Biol., 8, 176.
13. Segal, D.J., Beerli, R.R., Blancafort, P., Dreier, B., Effertz, K., Huber, A., Koksch, B., Lund, C.V., Magnenat, L., and Valente, D. et al. Segal, D.J., Beerli, R.R., Blancafort, P., Dreier, B., Effertz, K., Huber, A., Koksch, B., Lund, C.V., Magnenat, L., and Valente, D. (2003) Evaluation of a modular strategy for the construction of novel polydactyl zinc finger DNA-binding proteins. Biochemistry, 42, 2137-2148.
14. Beerli, R.R., Segal, D.J., Dreier, B., and Barbas, C.F. III Beerli, R.R., Segal, D.J., Dreier, B., and Barbas, C.F. III (1998) Toward controlling gene expression at will: specific regulation of the erbB-2/HER-2 promoter by using polydactyl zinc finger proteins constructed from modular building blocks. Proc. Natl. Acad. Sci. U.S.A., 95, 14628-14633.
15. Bhakta, M.S. and Segal, D.J.Bhakta, M.S. and Segal, D.J. (2010) The generation of zinc finger proteins by modular assembly. Methods Mol. Biol., 649, 3-30.
16. Segal, D.J. and Barbas, C.F.Segal, D.J. and Barbas, C.F. (1999) Design of novel sequence-specific DNA-binding proteins. Curr. Opin. Chem. Biol., 4, 34-39.
17. Dreier, B., Beerli, R.R., Segal, D.J., Flippin, J.D., and Barbas, C.F. IIIDreier, B., Beerli, R.R., Segal, D.J., Flippin, J.D., and Barbas, C.F. III (2001) Development of zinc finger domains for recognition of the 5′-ANN-3′ family of DNA sequences and their use in the construction of artificial transcription factors. J. Biol. Chem., 276, 29466-29478.
18. Elrod-Erickson, M., Rould, M.A., Nekludova, L., and Pabo, C.O.Elrod-Erickson, M., Rould, M.A., Nekludova, L., and Pabo, C.O. (1996) Zif268 protein-DNA complex refined at 1.6 A: a model system for understanding zinc finger-DNA interactions. Structure, 4, 1171-1180.
19. Frietze, S., O'Geen, H., Blahnik, K.R., Jin, V.X., and Farnham, P.J.Frietze, S., O'Geen, H., Blahnik, K.R., Jin, V.X., and Farnham, P.J. (2010) ZNF274 recruits the histone methyltransferase SETDB1 to the 3′ ends of ZNF genes. PloS One, 5, e15082.
20. Iyengar, S., Ivanov, A.V., Jin, V.X., Rauscher, F.J. III, and Farnham, P.J.Iyengar, S., Ivanov, A.V., Jin, V.X., Rauscher, F.J. III, and Farnham, P.J. (2011) Functional analysis of KAP1 genomic recruitment. Mol. Cell. Biol., 31, 1833-1847.
21. Gommans, W.M., McLaughlin, P.M., Lindhout, B.I., Segal, D.J., Wiegman, D.J., Haisma, H.J., van der Zaal, B.J., and Rots, M.G.Gommans, W.M., McLaughlin, P.M., Lindhout, B.I., Segal, D.J., Wiegman, D.J., Haisma, H.J., van der Zaal, B.J., and Rots, M.G. (2007) Engineering zinc finger protein transcription factors to downregulate the epithelial glycoprotein-2 promoter as a novel anti-cancer treatment. Mol. Carcinog., 46, 391-401.
22. Beltran, A.S. and Blancafort, P.Beltran, A.S. and Blancafort, P. (2011) Reactivation of MASPIN in non-small cell lung carcinoma (NSCLC) cells by artificial transcription factors (ATFs). Epigenetics, 6, 224-235.
23. Beltran, A., Parikh, S., Liu, Y., Cuevas, B.D., Johnson, G.L., Futscher, B.W., and Blancafort, P.Beltran, A., Parikh, S., Liu, Y., Cuevas, B.D., Johnson, G.L., Futscher, B.W., and Blancafort, P. (2007) Re-activation of a dormant tumor suppressor gene maspin by designed transcription factors. Oncogene, 26, 2791-2798.
24. Lara, H., Wang, Y., Beltran, A.S., Juarez-Moreno, K., Yuan, X., Kato, S., Leisewitz, A.V., Cuello Fredes, M., Licea, A.F., and Connolly, D.C. et al. Lara, H., Wang, Y., Beltran, A.S., Juarez-Moreno, K., Yuan, X., Kato, S., Leisewitz, A.V., Cuello Fredes, M., Licea, A.F., and Connolly, D.C. (2012) Targeting serous epithelial ovarian cancer with designer zinc finger transcription factors. J. Biol. Chem., 287, 29873-29886.
25. Chen, H., Kazemier, H.G., de Groote, M.L., Ruiters, M.H., Xu, G.L., and Rots, M.G.Chen, H., Kazemier, H.G., de Groote, M.L., Ruiters, M.H., Xu, G.L., and Rots, M.G. (2013) Induced DNA demethylation by targeting ten-eleven translocation 2 to the human ICAM-1 promoter. Nucleic Acids Res., 42, 1563-1574.
26. Rivenbark, A.G., Stolzenburg, S., Beltran, A.S., Yuan, X., Rots, M.G., Strahl, B.D., and Blancafort, P.Rivenbark, A.G., Stolzenburg, S., Beltran, A.S., Yuan, X., Rots, M.G., Strahl, B.D., and Blancafort, P. (2012) Epigenetic reprogramming of cancer cells via targeted DNA methylation. Epigenetics, 7, 350-360.
27. Stolzenburg, S., Rots, M.G., Beltran, A.S., Rivenbark, A.G., Yuan, X., Qian, H., Strahl, B.D., and Blancafort, P.Stolzenburg, S., Rots, M.G., Beltran, A.S., Rivenbark, A.G., Yuan, X., Qian, H., Strahl, B.D., and Blancafort, P. (2012) Targeted silencing of the oncogenic transcription factor SOX2 in breast cancer. Nucleic Acids Res., 40, 6725-6740.
28. Beltran, A.S., Sun, X., Lizardi, P.M., and Blancafort, P.Beltran, A.S., Sun, X., Lizardi, P.M., and Blancafort, P. (2008) Reprogramming epigenetic silencing: artificial transcription factors synergize with chromatin remodeling drugs to reactivate the tumor suppressor mammary serine protease inhibitor. Mol. Cancer Ther., 7, 1080-1090.
29. Gilbert, L.A., Larson, M.H., Morsut, L., Liu, Z., Brar, G.A., Torres, S.E., Stern-Ginossar, N., Brandman, O., Whitehead, E.H., and Doudna, J.A. et al. Gilbert, L.A., Larson, M.H., Morsut, L., Liu, Z., Brar, G.A., Torres, S.E., Stern-Ginossar, N., Brandman, O., Whitehead, E.H., and Doudna, J.A. (2013) Cell, 154, 442-451.
30. Mendenhall, E.M., Williamson, K.E., Reyon, D., Zou, J.Y., Ram, O., Joung, J.K., and Bernstein, B.E.Mendenhall, E.M., Williamson, K.E., Reyon, D., Zou, J.Y., Ram, O., Joung, J.K., and Bernstein, B.E. (2013) Locus-specific editing of histone modifications at endogenous enhancers. Nat. Biotechnol., 31, 1133-1136.
31. Wu, X., Scott, D.A., Kriz, A.J., Chiu, A.C., Hsu, P.D., Dadon, D.B., Cheng, A.W., Trevino, A.E., Konermann, S., and Chen, S. Wu, X., Scott, D.A., Kriz, A.J., Chiu, A.C., Hsu, P.D., Dadon, D.B., Cheng, A.W., Trevino, A.E., Konermann, S., and Chen, S. (2014) Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells. In: Nature Biotech., pp. 670-676.
32. O'Geen, H., Echipare, L., and Farnham, P.J.O'Geen, H., Echipare, L., and Farnham, P.J. (2011) Using ChIP-seq technology to generate high-resolution profiles of histone modifications. Methods Mol. Biol., 791, 265-286.
33. Langmead, B. and Salzberg, S.L.Langmead, B. and Salzberg, S.L. (2012) Fast gapped-read alignment with Bowtie 2. Nat. Methods, 9, 357-359.
34. Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., and Durbin, R.Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., and Durbin, R. (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics, 25, 2078-2079.
35. Quinlan, A.R. and Hall, I.M.Quinlan, A.R. and Hall, I.M. (2010) BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics, 26, 841-842.
36. Blahnik, K.R., Dou, L., O'Geen, H., McPhillips, T., Xu, X., Cao, A.R., Iyengar, S., Nicolet, C.M., Ludaescher, B., and Korf, I. et al. Blahnik, K.R., Dou, L., O'Geen, H., McPhillips, T., Xu, X., Cao, A.R., Iyengar, S., Nicolet, C.M., Ludaescher, B., and Korf, I. (2010) Sole-search: an integrated analysis program for peak detection and functional annotation using ChIP-seq data. Nucleic Acids Research, 38, e13.
37. Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y.C., Laslo, P., Cheng, J.X., Murre, C., Singh, H., and Glass, C.K.Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y.C., Laslo, P., Cheng, J.X., Murre, C., Singh, H., and Glass, C.K. (2010) Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell, 38, 576-589.
38. Trapnell, C., Pachter, L., and Salzberg, S.L.Trapnell, C., Pachter, L., and Salzberg, S.L. (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics, 25, 1105-1111.
39. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature, 489, 57-74.
40. (2011) A user's guide to the encyclopedia of DNA elements (ENCODE). PLoS Biol., 9, e1001046.
41. Consortium, T.E.Consortium, T.E. (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature, 447, 799-816.
42. (2004) The ENCODE (ENCyclopedia Of DNA Elements) Project. Science, 306, 636-640.
43. Urnov, F.D., Rebar, E.J., Holmes, M.C., Zhang, H.S., and Gregory, P.D.Urnov, F.D., Rebar, E.J., Holmes, M.C., Zhang, H.S., and Gregory, P.D. (2010) Genome editing with engineered zinc finger nucleases. Nature reviews. Genetics, 11, 636-646.
44. Ramirez, C.L., Foley, J.E., Wright, D.A., Muller-Lerch, F., Rahman, S.H., Cornu, T.I., Winfrey, R.J., Sander, J.D., Fu, F., and Townsend, J.A. et al. Ramirez, C.L., Foley, J.E., Wright, D.A., Muller-Lerch, F., Rahman, S.H., Cornu, T.I., Winfrey, R.J., Sander, J.D., Fu, F., and Townsend, J.A. (2008) Unexpected failure rates for modular assembly of engineered zinc fingers. Nat. Methods, 5, 374-375.
45. Margolin, J.F., Friedman, J.R., Meyer, W.K., Vissing, H., Thiesen, H.J., and Rauscher, F.J. IIIMargolin, J.F., Friedman, J.R., Meyer, W.K., Vissing, H., Thiesen, H.J., and Rauscher, F.J. III (1994) Kruppel-associated boxes are potent transcriptional repression domains. Proc. Natl. Acad. Sci. U.S.A., 91, 4509-4513.
46. Blahnik, K.R., Dou, L., Echipare, L., Iyengar, S., O'Geen, H., Sanchez, E., Zhao, Y., Marra, M.A., Hirst, M., and Costello, J.F. et al. Blahnik, K.R., Dou, L., Echipare, L., Iyengar, S., O'Geen, H., Sanchez, E., Zhao, Y., Marra, M.A., Hirst, M., and Costello, J.F. (2011) Characterization of the contradictory chromatin signatures at the 3′ exons of zinc finger genes. PloS One, 6, e17121.
47. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature, 489, 57-74.
48. Thurman, R.E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M.T., Haugen, E., Sheffield, N.C., Stergachis, A.B., Wang, H., and Vernot, B. et al. Thurman, R.E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M.T., Haugen, E., Sheffield, N.C., Stergachis, A.B., Wang, H., and Vernot, B. (2012) The accessible chromatin landscape of the human genome. Nature, 489, 75-82.
49. Frietze, S., Wang, R., Yao, L., Tak, Y.G., Ye, Z., Gaddis, M., Witt, H., Farnham, P.J., and Jin, V.X.Frietze, S., Wang, R., Yao, L., Tak, Y.G., Ye, Z., Gaddis, M., Witt, H., Farnham, P.J., and Jin, V.X. (2012) Cell type-specific binding patterns reveal that TCF7L2 can be tethered to the genome by association with GATA3. Genome Biol., 13, R52.
50. Iyengar, S. and Farnham, P.J.Iyengar, S. and Farnham, P.J. (2011) KAP1: an enigmatic master regulator of the genome. J. Biol. Chem., 286, 26267-26276.
51. Ivanov, A.V., Peng, H., Yurchenko, V., Yap, K.L., Negorev, D.G., Schultz, D.C., Psulkowski, E., Fredericks, W.J., White, D.E., and Maul, G.G. et al. Ivanov, A.V., Peng, H., Yurchenko, V., Yap, K.L., Negorev, D.G., Schultz, D.C., Psulkowski, E., Fredericks, W.J., White, D.E., and Maul, G.G. (2007) PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing. Mol. Cell, 28, 823-837.
52. Schultz, D.C., Ayyanathan, K., Negorev, D., Maul, G.G., and Rauscher, F.J. IIISchultz, D.C., Ayyanathan, K., Negorev, D., Maul, G.G., and Rauscher, F.J. III (2002) SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev., 16, 919-932.
53. Sripathy, S.P., Stevens, J., and Schultz, D.C.Sripathy, S.P., Stevens, J., and Schultz, D.C. (2006) The KAP1 corepressor functions to coordinate the assembly of de novo HP1-demarcated microenvironments of heterochromatin required for KRAB zinc finger protein-mediated transcriptional repression. Mol. Cell. Biol., 26, 8623-8638.
54. Groner, A.C., Meylan, S., Ciuffi, A., Zangger, N., Ambrosini, G., Denervaud, N., Bucher, P., and Trono, D.Groner, A.C., Meylan, S., Ciuffi, A., Zangger, N., Ambrosini, G., Denervaud, N., Bucher, P., and Trono, D. (2010) KRAB-zinc finger proteins and KAP1 can mediate long-range transcriptional repression through heterochromatin spreading. PLoS Genet., 6, e1000869.
55. Ayyanathan, K., Lechner, M.S., Bell, P., Maul, G.G., Schultz, D.C., Yamada, Y., Tanaka, K., Torigoe, K., and Rauscher, F.J. III Ayyanathan, K., Lechner, M.S., Bell, P., Maul, G.G., Schultz, D.C., Yamada, Y., Tanaka, K., Torigoe, K., and Rauscher, F.J. III (2003) Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation. Genes Dev., 17, 1855-1869.
56. Barde, I., Laurenti, E., Verp, S., Groner, A.C., Towne, C., Padrun, V., Aebischer, P., Trumpp, A., and Trono, D.Barde, I., Laurenti, E., Verp, S., Groner, A.C., Towne, C., Padrun, V., Aebischer, P., Trumpp, A., and Trono, D. (2009) Regulation of episomal gene expression by KRAB/KAP1-mediated histone modifications. J. Virol., 83, 5574-5580.
57. Perez-Pinera, P., Ousterout, D.G., Brunger, J.M., Farin, A.M., Glass, K.A., Guilak, F., Crawford, G.E., Hartemink, A.J., and Gersbach, C.A. Perez-Pinera, P., Ousterout, D.G., Brunger, J.M., Farin, A.M., Glass, K.A., Guilak, F., Crawford, G.E., Hartemink, A.J., and Gersbach, C.A. (2013) Synergistic and tunable human gene activation by combinations of synthetic transcription factors. Nat. Methods, 10, 239-242.
58. Perez-Pinera, P., Kocak, D.D., Vockley, C.M., Adler, A.F., Kabadi, A.M., Polstein, L.R., Thakore, P.I., Glass, K.A., Ousterout, D.G., and Leong, K.W. et al. Perez-Pinera, P., Kocak, D.D., Vockley, C.M., Adler, A.F., Kabadi, A.M., Polstein, L.R., Thakore, P.I., Glass, K.A., Ousterout, D.G., and Leong, K.W. (2013) RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat. Methods, 10, 973-976.
59. Ji, Q., Fischer, A.L., Brown, C.R., Eastlund, E.R., Dvash, T., Zhong, B., Gerber, M.A., Lyons, I., Knight, S.W., and Kreader, C.A.Ji, Q., Fischer, A.L., Brown, C.R., Eastlund, E.R., Dvash, T., Zhong, B., Gerber, M.A., Lyons, I., Knight, S.W., and Kreader, C.A. (2014) Engineered zinc-finger transcription factors activate OCT4 (POU5F1), SOX2, KLF4, c-MYC (MYC) and miR302/367. Nucleic Acids Res, 42, 6158-6167.
60. Chang, C.J., Chen, Y.L., and Lee, S.C.Chang, C.J., Chen, Y.L., and Lee, S.C. (1998) Coactivator TIF1beta interacts with transcription factor C/EBPbeta and glucocorticoid receptor to induce alpha1-acid glycoprotein gene expression. Mol. Cell. Biol., 18, 5880-5887.
61. Rooney, J.W. and Calame, K.L.Rooney, J.W. and Calame, K.L. (2001) TIF1beta functions as a coactivator for C/EBPbeta and is required for induced differentiation in the myelomonocytic cell line U937. Genes Dev., 15, 3023-3038.
62. Rambaud, J., Desroches, J., Balsalobre, A., and Drouin, J.Rambaud, J., Desroches, J., Balsalobre, A., and Drouin, J. (2009) TIF1beta/KAP-1 is a coactivator of the orphan nuclear receptor NGFI-B/Nur77. J. Biol. Chem., 284, 14147-14156.
63. Juarez-Moreno, K., Erices, R., Beltran, A.S., Stolzenburg, S., Cuello-Fredes, M., Owen, G.I., Qian, H., and Blancafort, P.Juarez-Moreno, K., Erices, R., Beltran, A.S., Stolzenburg, S., Cuello-Fredes, M., Owen, G.I., Qian, H., and Blancafort, P. (2013) Breaking through an epigenetic wall: Re-activation of Oct4 by KRAB-containing designer zinc finger transcription factors. Epigenetics, 8, 164-176.
64. Hsu, P.D., Scott, D.A., Weinstein, J.A., Ran, F.A., Konermann, S., Agarwala, V., Li, Y., Fine, E.J., Wu, X., and Shalem, O. et al. Hsu, P.D., Scott, D.A., Weinstein, J.A., Ran, F.A., Konermann, S., Agarwala, V., Li, Y., Fine, E.J., Wu, X., and Shalem, O. (2013) DNA targeting specificity of RNA-guided Cas9 nucleases. Nat. Biotechnol., 31, 827-832.
65. Kuscu, C., Arslan, S., Singh, R., Thorpe, J., and Adli, M.Kuscu, C., Arslan, S., Singh, R., Thorpe, J., and Adli, M. (2014) Genome-wide analysis reveals characteristics of off-target sites bound by the Cas9 endonuclease. Nat. Biotechnol., 32, 677-683.
66. Cho, S.W., Kim, S., Kim, Y., Kweon, J., Kim, H.S., Bae, S., and Kim, J.S.Cho, S.W., Kim, S., Kim, Y., Kweon, J., Kim, H.S., Bae, S., and Kim, J.S. (2014) Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases. Genome Res., 24, 132-141.