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Designing Zinc Finger Proteins for Applications in Synthetic Biology

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Systems and Synthetic Biology
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Abstract

Transcription factors capable of regulating the expression repertoire of a cell possessing specific recognition patterns dominating their interaction with its respective DNA, that can be exploited to achieve targeted genome engineering, happens to be the cynosure of most studies encompassing DNA-protein interaction. The mostly widely studied transcription factors are zinc finger proteins that bind to its target DNA via few cardinal residues on its alpha–helix, comprising each finger of the protein. Exploiting the binding specificity and affinity of the interaction between the zinc fingers and the respective DNA can help to generate engineered zinc fingers for therapeutic purposes involving genome targeting. Exploring the structure-function relationships of the existing zinc finger-DNA complexes can aid in predicting the probable zinc fingers that could bind to any target DNA. This chapter describes the interaction of the zinc finger with its respective DNA, its prospective manipulation and application in the field of engineering the genome, various prediction tools dealing with either machine learning or physicochemical parameters for designing customized zinc fingers for any target DNA.

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References

  • Beerli RR, Barbas CF 3rd (2002) Engineering polydactyl zinc-finger transcription factors. Nat Biotechnol 20(2):135–141

    Google Scholar 

  • Beerli RR, Dreier B et al (2000) Positive and negative regulation of endogenous genes by designed transcription factors. Proc Natl Acad Sci U S A 97(4):1495–1500

    Google Scholar 

  • Berg JM (1990) Zinc finger domains: hypotheses and current knowledge. Annu Rev Biophys Biophys Chem 19:405–421

    Google Scholar 

  • Burgess DJ (2013) Technology: a CRISPR genome-editing tool. Nat Rev Genet 14(2):80–81

    Google Scholar 

  • Carr PA, Church GM (2009) Genome engineering. Nat Biotechnol 27(12):1151–1162

    Google Scholar 

  • Cho SY, Chung M et al (2008) ZIFIBI: prediction of DNA binding sites for zinc finger proteins. Biochem Biophys Res Commun 369(3):845–848

    Google Scholar 

  • de Vries SJ van Dijk M et al (2010) The HADDOCK web server for data-driven biomolecular docking. Nat Protoc 5(5):883–897

    Google Scholar 

  • Dreier B, Fuller RP et al (2005) Development of zinc finger domains for recognition of the 5'-CNN-3` family DNA sequences and their use in the construction of artificial transcription factors. J Biol Chem 280(42):35588–35597

    Google Scholar 

  • Fairall L, Schwabe JW et al (1993) The crystal structure of a two zinc-finger peptide reveals an extension to the rules for zinc-finger/DNA recognition. Nature 366(6454):483–487

    Google Scholar 

  • Havranek JJ, Duarte CM et al (2004) A simple physical model for the prediction and design of protein-DNA interactions. J Mol Biol 344(1):59–70

    Google Scholar 

  • Isalan M, Choo Y, Klug A (1997) Synergy between adjacent zinc fingers in sequence-specific DNA recognition. Proc Natl Acad Sci 94(11):5617–5562

    Google Scholar 

  • Jayakanthan M, Muthukumaran J et al (2009) ZifBASE: a database of zinc finger proteins and associated resources. BMC Genomics 10:421

    Google Scholar 

  • Klug A (2005) Towards therapeutic applications of engineered zinc finger proteins. FEBS Lett 579(4):892–894

    Google Scholar 

  • Klug A (2010) The discovery of zinc fingers and their applications in gene regulation and genome manipulation. Annu Rev Biochem 79:213–231

    Google Scholar 

  • Li Y, Yang D et al (2008) ZNF418, a novel human KRAB/C2H2 zinc finger protein, suppresses MAPK signaling pathway. Mol Cell Biochem 310(1–2):141–151

    Google Scholar 

  • Maeder ML, Thibodeau-Beganny S et al (2008) Rapid “open-source” engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol Cell 31(2):294–301

    Google Scholar 

  • Mandel-Gutfreund Y, Baron A et al (2001) A structure-based approach for prediction of protein binding sites in gene upstream regions. Pac Symp Biocomput 6:139–150

    Google Scholar 

  • Mandell JG, Barbas CF 3rd (2006) Zinc Finger Tools: custom DNA-binding domains for transcription factors and nucleases. Nucleic Acids Res 34(Web Server issue):W516–523

    Google Scholar 

  • Miller J, McLachlan AD et al (1985) Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. EMBO J 4(6):1609–1614

    Google Scholar 

  • Miller JC, Tan SY et al (2011) A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 29(2):143-U149

    Google Scholar 

  • Molparia B, Goyal K et al (2010) ZiF-Predict: a web tool for predicting DNA-binding specificity in C2H2 zinc finger proteins. Genomics Proteomics Bioinformatics 8(2):122–126

    Google Scholar 

  • Pavletich NP, Pabo CO (1991) Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science 252(5007):809–817

    Google Scholar 

  • Pelham HR, Brown DD (1980) A specific transcription factor that can bind either the 5S RNA gene or 5S RNA. Proc Natl Acad Sci U S A 77(7):4170–4174

    Google Scholar 

  • Persikov AV, Osada R et al (2009) Predicting DNA recognition by Cys2His2 zinc finger proteins. Bioinformatics 25(1):22–29

    Google Scholar 

  • Ren DL, Collingwood TN et al (2002) PPAR gamma knockdown by engineered transcription factors: exogenous PPAR gamma 2 but not PPAR gamma 1 reactivates adipogenesis. Genes Dev 16(1):27–32

    Google Scholar 

  • Roy S, Dutta S et al (2012) Prediction of DNA-binding specificity in zinc finger proteins. J Biosci 37(3):483–491

    Google Scholar 

  • Sander JD, Zaback P et al (2007) Zinc Finger Targeter (ZiFiT): an engineered zinc finger/target site design tool. Nucleic Acids Res 35(Web Server issue):W599–605

    Google Scholar 

  • Sander JD, Dahlborg EJ et al (2011) Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat Methods 8(1):67–69

    Google Scholar 

  • Segal DJ, Dreier B et al (1999) Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5'-GNN-3` DNA target sequences. Proc Natl Acad Sci U S A 96(6):2758–2763

    Google Scholar 

  • Siggers TW, Honig B (2007) Structure-based prediction of C2H2 zinc-finger binding specificity: sensitivity to docking geometry. Nucleic Acids Res 35(4):1085–1097

    Google Scholar 

  • Takeuchi R, Lambert AR et al (2011) Tapping natural reservoirs of homing endonucleases for targeted gene modification. Proc Natl Acad Sci U S A 108(32):13077–13082

    Google Scholar 

  • Tian C, Xing GC et al (2009) KRAB-type zinc-finger protein Apak specifically regulates p53-dependent apoptosis. Nat Cell Biol 11(5):580–U122

    Google Scholar 

  • Wood AJ, Lo TW et al (2011) Targeted genome editing across species using ZFNs and TALENs. Science 333(6040):307

    Google Scholar 

  • Xu GL, Bestor TH (1997) Cytosine methylation targetted to pre-determined sequences. Nat Genet 17(4):376–378

    Google Scholar 

  • Zhang L, Spratt SK et al (2000) Synthetic zinc finger transcription factor action at an endogenous chromosomal site. Activation of the human erythropoietin gene. J Biol Chem 275(43):33850–33860

    Google Scholar 

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Acknowledgement

The work on zinc finger proteins in the laboratory of DS is supported by grants from Lady Tata Memorial Trust, DuPont and Department of Biotechnology (DBT), Govt. of India, under the IYBA & National Bioscience Award schemes. SD is a recipient of DST INSPIRE Fellowship for her doctoral studies in the laboratory of DS.

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Correspondence to Durai Sundar .

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Dutta, S., Sundar, D. (2015). Designing Zinc Finger Proteins for Applications in Synthetic Biology. In: Singh, V., Dhar, P. (eds) Systems and Synthetic Biology. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9514-2_15

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