Systematic transfer of prokaryotic sensors and circuits to mammalian cells

ACS Synthetic Biology

Volumn 3, Issue 12, 2014, Pages 880-891

  Stanton, Brynne C ^a   Siciliano, Velia ^a   Ghodasara, Amar ^a   Wroblewska, Liliana ^a   Clancy, Kevin ^b   Trefzer, Axel C ^b   Chesnut, Jonathan D ^b   Weiss, Ron ^a   Voigt, Christopher A ^a  

^a Massachusetts Institute of Technology Cambridge   (United States)

^b Thermo Fisher Scientific   (United States)

Author keywords

2,4 diacetylphloroglucinol (DAPG); eukaryote; inducible system; mammalian synthetic biology; systems biology

Indexed keywords

REGULATOR PROTEIN; REPRESSOR PROTEIN; TETR PROTEIN; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; 2,4-DIACETYLPHLOROGLUCINOL; ESCHERICHIA COLI PROTEIN; PHLOROGLUCINOL; TETR(B) PROTEIN, E COLI;

AMINO ACID SEQUENCE; ANIMAL CELL; ARTICLE; CHO CELL LINE; ESCHERICHIA COLI; FEMALE; HEK293 CELL LINE; HUMAN; HUMAN CELL; MAMMAL CELL; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; OPERATOR GENE; PROTEIN DNA BINDING; REPRESSOR GENE; ANALOGS AND DERIVATIVES; ANIMAL; BACTERIAL GENE; CRICETULUS; GENETIC ENGINEERING; GENETICS; HAMSTER; PROCEDURES; PROMOTER REGION; SYNTHETIC BIOLOGY; TRANSGENE;

CRICETULUS GRISEUS; ESCHERICHIA COLI; EUKARYOTA; MAMMALIA; PROKARYOTA;

ANIMALS; CHO CELLS; CRICETINAE; CRICETULUS; ESCHERICHIA COLI; ESCHERICHIA COLI PROTEINS; GENES, BACTERIAL; GENETIC ENGINEERING; HEK293 CELLS; HUMANS; PHLOROGLUCINOL; PROMOTER REGIONS, GENETIC; SYNTHETIC BIOLOGY; TRANSGENES;

EID: 84919633247     PISSN: None     EISSN: 21615063     Source Type: Journal    
DOI: 10.1021/sb5002856     Document Type: Article

References (118)

1. Fischbach, M. A., Bluestone, J. A., and Lim, W. A. (2013) Cell-based therapeutics: The next pillar of medicine Sci. Transl. Med. 5, 179ps177
2. Bacchus, W., Aubel, D., and Fussenegger, M. (2013) Biomedically relevant circuit-design strategies in mammalian synthetic biology Mol. Syst. Biol. 9, 691
3. Chen, Y. Y. and Smolke, C. D. (2011) From DNA to targeted therapeutics: Bringing synthetic biology to the clinic Sci. Transl. Med. 3, 106ps142
4. Slusarczyk, A. L., Lin, A., and Weiss, R. (2012) Foundations for the design and implementation of synthetic genetic circuits Nat. Rev. Genet. 13, 406-420
5. Fussenegger, M., Schlatter, S., Datwyler, D., Mazur, X., and Bailey, J. E. (1998) Controlled proliferation by multigene metabolic engineering enhances the productivity of Chinese hamster ovary cells Nat. Biotechnol. 16, 468-472
6. Wurm, F. M. (2004) Production of recombinant protein therapeutics in cultivated mammalian cells Nat. Biotechnol. 22, 1393-1398
7. Weber, W. and Fussenegger, M. (2007) Inducible product gene expression technology tailored to bioprocess engineering Curr. Opin. Biotechnol. 18, 399-410
8. Wieland, M. and Fussenegger, M. (2012) Reprogrammed cell delivery for personalized medicine Adv. Drug Delivery Rev. 64, 1477-1487
9. Weber, W. and Fussenegger, M. (2009) The impact of synthetic biology on drug discovery Drug Delivery Rev. 14, 956-963
10. Nielsen, A. A., Segall-Shapiro, T. H., and Voigt, C. A. (2013) Advances in genetic circuit design: Novel biochemistries, deep part mining, and precision gene expression Curr. Opin. Chem. Biol. 17, 878-892
11. Ruder, W. C., Lu, T., and Collins, J. J. (2011) Synthetic biology moving into the clinic Science 333, 1248-1252
12. Ramos, J. L., Martinez-Bueno, M., Molina-Henares, A. J., Teran, W., Watanabe, K., Zhang, X., Gallegos, M. T., Brennan, R., and Tobes, R. (2005) The TetR family of transcriptional repressors Microbiol. Mol. Biol. Rev.: MMBR 69, 326-356
13. Cuthbertson, L. and Nodwell, J. R. (2013) The TetR family of regulators Microbiol. Mol. Biol. Rev.: MMBR 77, 440-475
14. Stanton, B. C., Nielsen, A. A., Tamsir, A., Clancy, K., Peterson, T., and Voigt, C. A. (2014) Genomic mining of prokaryotic repressors for orthogonal logic gates Nat. Chem. Biol. 10, 99-105
15. Gossen, M. and Bujard, H. (1992) Tight control of gene expression in mammalian cells by tetracycline-responsive promoters Proc. Natl. Acad. Sci. U.S.A. 89, 5547-5551
16. Gossen, M., Freundlieb, S., Bender, G., Muller, G., Hillen, W., and Bujard, H. (1995) Transcriptional activation by tetracyclines in mammalian cells Science 268, 1766-1769
17. Agha-Mohammadi, S. and Lotze, M. T. (2000) Regulatable systems: Applications in gene therapy and replicating viruses J. Clin. Invest. 105, 1177-1183
18. Urlinger, S., Baron, U., Thellmann, M., Hasan, M. T., Bujard, H., and Hillen, W. (2000) Exploring the sequence space for tetracycline-dependent transcriptional activators: Novel mutations yield expanded range and sensitivity Proc. Natl. Acad. Sci. U.S.A. 97, 7963-7968
19. Vieyra, D. S. and Goodell, M. A. (2007) Pluripotentiality and conditional transgene regulation in human embryonic stem cells expressing insulated tetracycline-ON transactivator Stem Cells 25, 2559-2566
20. Wu, Z., Chen, J., Ren, J., Bao, L., Liao, J., Cui, C., Rao, L., Li, H., Gu, Y., Dai, H., Zhu, H., Teng, X., Cheng, L., and Xiao, L. (2009) Generation of pig induced pluripotent stem cells with a drug-inducible system J. Mol. Cell Biol. 1, 46-54
21. Zhao, X., Yu, Y., Zhao, Z., Guo, J., Fu, L., Yu, T., Hou, L., Yi, S., and Chen, W. (2012) Establishment of tetracycline-inducible, survivin-expressing CHO cell lines by an optimized screening method Biosci., Biotechnol., Biochem. 76, 1909-1912
22. Jones, J., Nivitchanyong, T., Giblin, C., Ciccarone, V., Judd, D., Gorfien, S., Krag, S. S., and Betenbaugh, M. J. (2005) Optimization of tetracycline-responsive recombinant protein production and effect on cell growth and ER stress in mammalian cells Biotechnol. Bioeng. 91, 722-732
23. Forster, K., Helbl, V., Lederer, T., Urlinger, S., Wittenburg, N., and Hillen, W. (1999) Tetracycline-inducible expression systems with reduced basal activity in mammalian cells Nucleic Acids Res. 27, 708-710
24. Zhang, J., Wang, C., Ke, N., Bliesath, J., Chionis, J., He, Q. S., Li, Q. X., Chatterton, J. E., Wong-Staal, F., and Zhou, D. (2007) A more efficient RNAi inducible system for tight regulation of gene expression in mammalian cells and xenograft animals RNA 13, 1375-1383
25. Saez, E., No, D., West, A., and Evans, R. M. (1997) Inducible gene expression in mammalian cells and transgenic mice Curr. Opin. Biotechnol. 8, 608-616
26. Auslander, S. and Fussenegger, M. (2013) From gene switches to mammalian designer cells: Present and future prospects Trends Biotechnol. 31, 155-168
27. Weber, W., Fux, C., Daoud-el Baba, M., Keller, B., Weber, C. C., Kramer, B. P., Heinzen, C., Aubel, D., Bailey, J. E., and Fussenegger, M. (2002) Macrolide-based transgene control in mammalian cells and mice Nat. Biotechnol. 20, 901-907
28. Fussenegger, M., Morris, R. P., Fux, C., Rimann, M., von Stockar, B., Thompson, C. J., and Bailey, J. E. (2000) Streptogramin-based gene regulation systems for mammalian cells Nat. Biotechnol. 18, 1203-1208
29. Mullick, A., Xu, Y., Warren, R., Koutroumanis, M., Guilbault, C., Broussau, S., Malenfant, F., Bourget, L., Lamoureux, L., Lo, R., Caron, A. W., Pilotte, A., and Massie, B. (2006) The cumate gene-switch: A system for regulated expression in mammalian cells BMC Biotechnol. 6, 43
30. Weber, W., Rimann, M., Spielmann, M., Keller, B., Daoud-El Baba, M., Aubel, D., Weber, C. C., and Fussenegger, M. (2004) Gas-inducible transgene expression in mammalian cells and mice Nat. Biotechnol. 22, 1440-1444
31. Malphettes, L., Weber, C. C., El-Baba, M. D., Schoenmakers, R. G., Aubel, D., Weber, W., and Fussenegger, M. (2005) A novel mammalian expression system derived from components coordinating nicotine degradation in arthrobacter nicotinovorans pAO1 Nucleic Acids Res. 33, e107
32. Weber, W., Schoenmakers, R., Spielmann, M., El-Baba, M. D., Folcher, M., Keller, B., Weber, C. C., Link, N., van de Wetering, P., Heinzen, C., Jolivet, B., Sequin, U., Aubel, D., Thompson, C. J., and Fussenegger, M. (2003) Streptomyces-derived quorum-sensing systems engineered for adjustable transgene expression in mammalian cells and mice Nucleic Acids Res. 31, e71
33. Neddermann, P., Gargioli, C., Muraglia, E., Sambucini, S., Bonelli, F., De Francesco, R., and Cortese, R. (2003) A novel, inducible, eukaryotic gene expression system based on the quorum-sensing transcription factor TraR EMBO Rep. 4, 159-165
34. Miller, M., Hafner, M., Sontag, E., Davidsohn, N., Subramanian, S., Purnick, P. E., Lauffenburger, D., and Weiss, R. (2012) Modular design of artificial tissue homeostasis: Robust control through synthetic cellular heterogeneity PLoS Comput. Biol. 8, e1002579
35. Hartenbach, S., Daoud-El Baba, M., Weber, W., and Fussenegger, M. (2007) An engineered l -arginine sensor of Chlamydia pneumoniae enables arginine-adjustable transcription control in mammalian cells and mice Nucleic Acids Res. 35, e136
36. Bacchus, W., Weber, W., and Fussenegger, M. (2013) Increasing the dynamic control space of mammalian transcription devices by combinatorial assembly of homologous regulatory elements from different bacterial species Metab. Eng. 15, 144-150
37. Gitzinger, M., Kemmer, C., Fluri, D. A., El-Baba, M. D., Weber, W., and Fussenegger, M. (2012) The food additive vanillic acid controls transgene expression in mammalian cells and mice Nucleic Acids Res. 40, e37
38. Gitzinger, M., Kemmer, C., El-Baba, M. D., Weber, W., and Fussenegger, M. (2009) Controlling transgene expression in subcutaneous implants using a skin lotion containing the apple metabolite phloretin Proc. Natl. Acad. Sci. U.S.A. 106, 10638-10643
39. Weber, W., Lienhart, C., Baba, M. D., and Fussenegger, M. (2009) A biotin-triggered genetic switch in mammalian cells and mice Metab. Eng. 11, 117-124
40. Weber, W., Stelling, J., Rimann, M., Keller, B., Daoud-El Baba, M., Weber, C. C., Aubel, D., and Fussenegger, M. (2007) A synthetic time-delay circuit in mammalian cells and mice Proc. Natl. Acad. Sci. U.S.A. 104, 2643-2648
41. Kemmer, C., Gitzinger, M., Daoud-El Baba, M., Djonov, V., Stelling, J., and Fussenegger, M. (2010) Self-sufficient control of urate homeostasis in mice by a synthetic circuit Nat. Biotechnol. 28, 355-360
42. Weber, W., Schoenmakers, R., Keller, B., Gitzinger, M., Grau, T., Daoud-El Baba, M., Sander, P., and Fussenegger, M. (2008) A synthetic mammalian gene circuit reveals antituberculosis compounds Proc. Natl. Acad. Sci. U.S.A. 105, 9994-9998
43. Wieland, M. and Fussenegger, M. (2012) Engineering molecular circuits using synthetic biology in mammalian cells Annu. Rev. Chem. Biomol. Eng. 3, 209-234
44. Deans, T. L., Cantor, C. R., and Collins, J. J. (2007) A tunable genetic switch based on RNAi and repressor proteins for regulating gene expression in mammalian cells Cell 130, 363-372
45. Kramer, B. P. and Fussenegger, M. (2005) Hysteresis in a synthetic mammalian gene network Proc. Natl. Acad. Sci. U.S.A. 102, 9517-9522
46. Kramer, B. P., Viretta, A. U., Daoud-El-Baba, M., Aubel, D., Weber, W., and Fussenegger, M. (2004) An engineered epigenetic transgene switch in mammalian cells Nat. Biotechnol. 22, 867-870
47. Kramer, B. P., Weber, W., and Fussenegger, M. (2003) Artificial regulatory networks and cascades for discrete multilevel transgene control in mammalian cells Biotechnol. Bioeng. 83, 810-820
48. Zhao, W., Bonem, M., McWhite, C., Silberg, J. J., and Segatori, L. (2014) Sensitive detection of proteasomal activation using the Deg-On mammalian synthetic gene circuit Nat. Commun. 5, 3612
49. Auslander, S., Auslander, D., Muller, M., Wieland, M., and Fussenegger, M. (2012) Programmable single-cell mammalian biocomputers Nature 487, 123-127
50. Leisner, M., Bleris, L., Lohmueller, J., Xie, Z., and Benenson, Y. (2010) Rationally designed logic integration of regulatory signals in mammalian cells Nat. Nanotechnol. 5, 666-670
51. Xie, Z., Wroblewska, L., Prochazka, L., Weiss, R., and Benenson, Y. (2011) Multi-input RNAi-based logic circuit for identification of specific cancer cells Science 333, 1307-1311
52. Tigges, M., Marquez-Lago, T. T., Stelling, J., and Fussenegger, M. (2009) A tunable synthetic mammalian oscillator Nature 457, 309-312
53. Tigges, M., Denervaud, N., Greber, D., Stelling, J., and Fussenegger, M. (2010) A synthetic low-frequency mammalian oscillator Nucleic Acids Res. 38, 2702-2711
54. Burrill, D. R., Inniss, M. C., Boyle, P. M., and Silver, P. A. (2012) Synthetic memory circuits for tracking human cell fate Genes Dev. 26, 1486-1497
55. Bacchus, W., Lang, M., El-Baba, M. D., Weber, W., Stelling, J., and Fussenegger, M. (2012) Synthetic two-way communication between mammalian cells Nat. Biotechnol. 30, 991-996
56. Weber, W., Schuetz, M., Denervaud, N., and Fussenegger, M. (2009) A synthetic metabolite-based mammalian inter-cell signaling system Mol. BioSyst. 5, 757-763
57. Weber, W., Kramer, B. P., and Fussenegger, M. (2007) A genetic time-delay circuitry in mammalian cells Biotechnol. Bioeng. 98, 894-902
58. Kramer, B. P., Fischer, C., and Fussenegger, M. (2004) BioLogic gates enable logical transcription control in mammalian cells Biotechnol. Bioeng. 87, 478-484
59. Folcher, M., Xie, M., Spinnler, A., and Fussenegger, M. (2013) Synthetic mammalian trigger-controlled bipartite transcription factors Nucleic Acids Res. 41, e134
60. Hurt, J. A., Thibodeau, S. A., Hirsh, A. S., Pabo, C. O., and Joung, J. K. (2003) Highly specific zinc finger proteins obtained by directed domain shuffling and cell-based selection Proc. Natl. Acad. Sci. U.S.A. 100, 12271-12276
61. Boch, J., Scholze, H., Schornack, S., Landgraf, A., Hahn, S., Kay, S., Lahaye, T., Nickstadt, A., and Bonas, U. (2009) Breaking the code of DNA binding specificity of TAL-type III effectors Science 326, 1509-1512
62. Qi, L. S., Larson, M. H., Gilbert, L. A., Doudna, J. A., Weissman, J. S., Arkin, A. P., and Lim, W. A. (2013) Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression Cell 152, 1173-1183
63. Gilbert, L. A., Larson, M. H., Morsut, L., Liu, Z., Brar, G. A., Torres, S. E., Stern-Ginossar, N., Brandman, O., Whitehead, E. H., Doudna, J. A., Lim, W. A., Weissman, J. S., and Qi, L. S. (2013) CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes Cell 154, 442-451
64. Khalil, A. S., Lu, T. K., Bashor, C. J., Ramirez, C. L., Pyenson, N. C., Joung, J. K., and Collins, J. J. (2012) A synthetic biology framework for programming eukaryotic transcription functions Cell 150, 647-658
65. Zhang, F., Cong, L., Lodato, S., Kosuri, S., Church, G. M., and Arlotta, P. (2011) Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription Nat. Biotechnol. 29, 149-153
66. Garg, A., Lohmueller, J. J., Silver, P. A., and Armel, T. Z. (2012) Engineering synthetic TAL effectors with orthogonal target sites Nucleic Acids Res. 40, 7584-7595
67. Kiani, S., Beal, J., Ebrahimkhani, M. R., Huh, J., Hall, R. N., Xie, Z., Li, Y., and Weiss, R. (2014) CRISPR transcriptional repression devices and layered circuits in mammalian cells Nat. Methods 11, 723-726
68. Gaber, R., Lebar, T., Majerle, A., Ster, B., Dobnikar, A., Bencina, M., and Jerala, R. (2014) Designable DNA-binding domains enable construction of logic circuits in mammalian cells Nat. Chem. Biol. 10, 203-208
69. Maeder, M. L., Linder, S. J., Cascio, V. M., Fu, Y., Ho, Q. H., and Joung, J. K. (2013) CRISPR RNA-guided activation of endogenous human genes Nat. Methods 10, 977-979
70. Mali, P., Aach, J., Stranges, P. B., Esvelt, K. M., Moosburner, M., Kosuri, S., Yang, L., and Church, G. M. (2013) CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering Nat. Biotechnol. 31, 833-838
71. 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., Leong, K. W., Guilak, F., Crawford, G. E., Reddy, T. E., and Gersbach, C. A. (2013) RNA-guided gene activation by CRISPR-Cas9-based transcription factors Nat. Methods 10, 973-976
72. Farzadfard, F., Perli, S. D., and Lu, T. K. (2013) Tunable and multifunctional eukaryotic transcription factors based on CRISPR/Cas ACS Synth. Biol. 2, 604-613
73. Rivera, V. M., Clackson, T., Natesan, S., Pollock, R., Amara, J. F., Keenan, T., Magari, S. R., Phillips, T., Courage, N. L., Cerasoli, F., Jr., Holt, D. A., and Gilman, M. (1996) A humanized system for pharmacologic control of gene expression Nat. Med. 2, 1028-1032
74. Beerli, R. R., Schopfer, U., Dreier, B., and Barbas, C. F., 3rd. (2000) Chemically regulated zinc finger transcription factors J. Biol. Chem. 275, 32617-32627
75. Li, Y., Moore, R., Guinn, M., and Bleris, L. (2012) Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression Sci. Rep. 2, 897
76. Konermann, S., Brigham, M. D., Trevino, A. E., Hsu, P. D., Heidenreich, M., Cong, L., Platt, R. J., Scott, D. A., Church, G. M., and Zhang, F. (2013) Optical control of mammalian endogenous transcription and epigenetic states Nature 500, 472-476
77. Polstein, L. R. and Gersbach, C. A. (2012) Light-inducible spatiotemporal control of gene activation by customizable zinc finger transcription factors J. Am. Chem. Soc. 134, 16480-16483
78. Li, Y., J, Y., Chen, H., Liao, W., Weiss, R., and Xie, Z. Modular construction of synthetic circuits using TALE transcriptional repressors in mammalian cells. Nat. Chem. Biol. 2014, under review
79. Banaszynski, L. A., Chen, L. C., Maynard-Smith, L. A., Ooi, A. G., and Wandless, T. J. (2006) A rapid, reversible, and tunable method to regulate protein function in living cells using synthetic small molecules Cell 126, 995-1004
80. Sadowski, I., Ma, J., Triezenberg, S., and Ptashne, M. (1988) GAL4-VP16 is an unusually potent transcriptional activator Nature 335, 563-564
81. Kim, D. W., Uetsuki, T., Kaziro, Y., Yamaguchi, N., and Sugano, S. (1990) Use of the human elongation factor 1 α promoter as a versatile and efficient expression system Gene 91, 217-223
82. Guye, P., Li, Y., Wroblewska, L., Duportet, X., and Weiss, R. (2013) Rapid, modular, and reliable construction of complex mammalian gene circuits Nucleic Acids Res. 41, e156
83. Loser, P., Jennings, G. S., Strauss, M., and Sandig, V. (1998) Reactivation of the previously silenced cytomegalovirus major immediate-early promoter in the mouse liver: Involvement of NFkappaB J. Virol. 72, 180-190
84. Livet, J., Weissman, T. A., Kang, H., Draft, R. W., Lu, J., Bennis, R. A., Sanes, J. R., and Lichtman, J. W. (2007) Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system Nature 450, 56-62
85. Schnider-Keel, U., Seematter, A., Maurhofer, M., Blumer, C., Duffy, B., Gigot-Bonnefoy, C., Reimmann, C., Notz, R., Defago, G., Haas, D., and Keel, C. (2000) Autoinduction of 2,4-diacetylphloroglucinol biosynthesis in the biocontrol agent Pseudomonas fluorescens CHA0 and repression by the bacterial metabolites salicylate and pyoluteorin J. Bacteriol. 182, 1215-1225
86. Bangera, M. G. and Thomashow, L. S. (1999) Identification and characterization of a gene cluster for synthesis of the polyketide antibiotic 2,4-diacetylphloroglucinol from Pseudomonas fluorescens Q2-87 J. Bacteriol. 181, 3155-3163
87. Crabtree, B. (1976) Theoretical considerations of the sensitivity conferred by substrate cycles in vivo Biochem. Soc. Trans. 4, 999-1002
88. Weiss, R. (2001) Cellular Computation and Communications Using Engineered Genetic Regulatory Networks, p 1, Massachusetts Institute of Technology, Cambridge, MA.
89. Yokobayashi, Y., Weiss, R., and Arnold, F. H. (2002) Directed evolution of a genetic circuit Proc. Natl. Acad. Sci. U.S.A. 99, 16587-16591
90. Tamsir, A., Tabor, J. J., and Voigt, C. A. (2011) Robust multicellular computing using genetically encoded NOR gates and chemical wires Nature 469, 212-215
91. Kelly, J. R., Rubin, A. J., Davis, J. H., Ajo-Franklin, C. M., Cumbers, J., Czar, M. J., de Mora, K., Glieberman, A. L., Monie, D. D., and Endy, D. (2009) Measuring the activity of BioBrick promoters using an in vivo reference standard J. Biol. Eng. 3, 4
92. Moon, T. S., Lou, C., Tamsir, A., Stanton, B. C., and Voigt, C. A. (2012) Genetic programs constructed from layered logic gates in single cells Nature 491, 249-253
93. Lou, C., Stanton, B., Chen, Y. J., Munsky, B., and Voigt, C. A. (2012) Ribozyme-based insulator parts buffer synthetic circuits from genetic context Nat. Biotechnol. 30, 1137-1142
94. Davidsohn, N., Beal, J., Kiani, S., Adler, A., Yaman, F., Li, Y., Xie, Z., and Weiss, R. (2014) Accurate predictions of genetic circuit behavior from part characterization and modular composition ACS Synth. Biol. 10.1021/sb500263b
95. Anderson, J. C., Voigt, C. A., and Arkin, A. P. (2007) Environmental signal integration by a modular AND gate Mol. Syst. Biol. 3, 133
96. Arkin, A. P. (2001) Synthetic cell biology Curr. Opin. Biotechnol. 12, 638-644
97. Purcell, O. and Lu, T. K. (2014) Synthetic analog and digital circuits for cellular computation and memory Curr. Opin. Biotechnol. 29C, 146-155
98. Xie, Z. L., Shao, S. L., Lv, J. W., Wang, C. H., Yuan, C. Z., Zhang, W. W., and Xu, X. J. (2011) Co-transfection and tandem transfection of HEK293A cells for overexpression and RNAi experiments Cell Biol. Int. 35, 187-192
99. Atchison, M. L. (1988) Enhancers: Mechanisms of action and cell specificity Annu. Rev. Cell Biol. 4, 127-153
100. Garnett, A. T., Square, T. A., and Medeiros, D. M. (2012) BMP, Wnt, and FGF signals are integrated through evolutionarily conserved enhancers to achieve robust expression of Pax3 and Zic genes at the zebrafish neural plate border Development 139, 4220-4231
101. Erceg, J., Saunders, T. E., Girardot, C., Devos, D. P., Hufnagel, L., and Furlong, E. E. (2014) Subtle changes in motif positioning cause tissue-specific effects on robustness of an enhancers activity PLoS Genet. 10, e1004060
102. Gossett, L. A., Kelvin, D. J., Sternberg, E. A., and Olson, E. N. (1989) A new myocyte-specific enhancer-binding factor that recognizes a conserved element associated with multiple muscle-specific genes Mol. Cell. Biol. 9, 5022-5033
103. Murtha, M., Tokcaer-Keskin, Z., Tang, Z., Strino, F., Chen, X., Wang, Y., Xi, X., Basilico, C., Brown, S., Bonneau, R., Kluger, Y., and Dailey, L. (2014) FIREWACh: High-throughput functional detection of transcriptional regulatory modules in mammalian cells Nat. Methods 11, 559-565
104. Dickel, D. E., Zhu, Y., Nord, A. S., Wylie, J. N., Akiyama, J. A., Afzal, V., Plajzer-Frick, I., Kirkpatrick, A., Gottgens, B., Bruneau, B. G., Visel, A., and Pennacchio, L. A. (2014) Function-based identification of mammalian enhancers using site-specific integration Nat. Methods 11, 566-571
105. Tuan, D. Y., Solomon, W. B., London, I. M., and Lee, D. P. (1989) An erythroid-specific, developmental-stage-independent enhancer far upstream of the human beta-like globingenes Proc. Natl. Acad. Sci. U.S.A. 86, 2554-2558
106. Fraser, P., Hurst, J., Collis, P., and Grosveld, F. (1990) DNaseI hypersensitive sites 1, 2, and 3 of the human beta-globin dominant control region direct position-independent expression Nucleic Acids Res. 18, 3503-3508
107. Hug, B. A., Moon, A. M., and Ley, T. J. (1992) Structure and function of the murine beta-globin locus control region 5 HS-3 Nucleic Acids Res. 20, 5771-5778
108. Way, J. C., Collins, J. J., Keasling, J. D., and Silver, P. A. (2014) Integrating biological redesign: Where synthetic biology came from and where it needs to go Cell 157, 151-161
109. Fath, S., Bauer, A. P., Liss, M., Spriestersbach, A., Maertens, B., Hahn, P., Ludwig, C., Schafer, F., Graf, M., and Wagner, R. (2011) Multiparameter RNA and codon optimization: A standardized tool to assess and enhance autologous mammalian gene expression PloS One 6, e17596
110. Hartley, J. L., Temple, G. F., and Brasch, M. A. (2000) DNA cloning using in vitro site-specific recombination Genome Res. 10, 1788-1795
111. Das, A. T., Zhou, X., Vink, M., Klaver, B., Verhoef, K., Marzio, G., and Berkhout, B. (2004) Viral evolution as a tool to improve the tetracycline-regulated gene expression system J. Biol. Chem. 279, 18776-18782
112. Nolden, L., Ngouoto-Nkili, C. E., Bendt, A. K., Kramer, R., and Burkovski, A. (2001) Sensing nitrogen limitation in Corynebacterium glutamicum: The role of glnK and glnD Molecular Microbiol. 42, 1281-1295
113. Shaw, G. C. and Fulco, A. J. (1993) Inhibition by barbiturates of the binding of Bm3R1 repressor to its operator site on the barbiturate-inducible cytochrome P450BM-3 gene of Bacillus megaterium J. Biol. Chem. 268, 2997-3004
114. Jeng, W. Y., Ko, T. P., Liu, C. I., Guo, R. T., Liu, C. L., Shr, H. L., and Wang, A. H. (2008) Crystal structure of IcaR, a repressor of the TetR family implicated in biofilm formation in Staphylococcus epidermidis Nucleic Acids Res. 36, 1567-1577
115. Murata, M., Ohno, S., Kumano, M., Yamane, K., and Ohki, R. (2003) Multidrug resistant phenotype of Bacillus subtilis spontaneous mutants isolated in the presence of puromycin and lincomycin Can. J. Microbiol. 49, 71-77
116. Rey, D. A., Puhler, A., and Kalinowski, J. (2003) The putative transcriptional repressor McbR, member of the TetR-family, is involved in the regulation of the metabolic network directing the synthesis of sulfur containing amino acids in Corynebacterium glutamicum J. Biotechnol. 103, 51-65
117. Grkovic, S., Hardie, K. M., Brown, M. H., and Skurray, R. A. (2003) Interactions of the QacR multidrug-binding protein with structurally diverse ligands: Implications for the evolution of the binding pocket Biochemistry 42, 15226-15236
118. Bryan, L. (1984) Antimicrobial Drug Resistance, Elsevier Science, Amsterdam.