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Zinc Fingers, TALEs, and CRISPR Systems: A Comparison of Tools for Epigenome Editing

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Epigenome Editing

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1767))

Abstract

The completion of genome, epigenome, and transcriptome mapping in multiple cell types has created a demand for precision biomolecular tools that allow researchers to functionally manipulate DNA, reconfigure chromatin structure, and ultimately reshape gene expression patterns. Epigenetic editing tools provide the ability to interrogate the relationship between epigenetic modifications and gene expression. Importantly, this information can be exploited to reprogram cell fate for both basic research and therapeutic applications. Three different molecular platforms for epigenetic editing have been developed: zinc finger proteins (ZFs), transcription activator-like effectors (TALEs), and the system of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins. These platforms serve as custom DNA-binding domains (DBDs), which are fused to epigenetic modifying domains to manipulate epigenetic marks at specific sites in the genome. The addition and/or removal of epigenetic modifications reconfigures local chromatin structure, with the potential to provoke long-lasting changes in gene transcription. Here we summarize the molecular structure and mechanism of action of ZF, TALE, and CRISPR platforms and describe their applications for the locus-specific manipulation of the epigenome. The advantages and disadvantages of each platform will be discussed with regard to genomic specificity, potency in regulating gene expression, and reprogramming cell phenotypes, as well as ease of design, construction, and delivery. Finally, we outline potential applications for these tools in molecular biology and biomedicine and identify possible barriers to their future clinical implementation.

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Acknowledgments

C.M. is a recipient of the Hackett Postgraduate Research Scholarship from the University of Western Australia. M.A. is a recipient of the Curtin Strategic International Research Scholarship. This work was supported by the Harry Perkins Institute of Medical Research, the University of Western Australia, and the following grants awarded to P.B.: the Australian Research Council DP150104433, FT130101688, and FT130101767; the Cancer Council Western Australia Research Fellowship; the National Health and Medical Research Council grant APP1069308; the National Institutes of Health grants R01CA170370 and R01DA036906; and the National Breast Cancer Foundation NC-14-024. Charlene Babra Waryah and Colette Moses contributed equally to this work. The authors apologize to those whose important contributions were omitted due to space constraints.

Contributions: C.B.W., C.M., and P.B. wrote the review; M.A. conducted structural modeling for Figs. 1 and 2.

Conflict of interest: The authors declare no conflicts of interest. The authorship of this article complies with the Australian Code of Responsible Conduct of Research.

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Author notes

  1. Charlene Babra Waryah and Colette Moses contributed equally to this work.

Authors and Affiliations

  1. Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, Nedlands, Perth, WA, Australia

    Charlene Babra Waryah, Colette Moses, Mahira Arooj & Pilar Blancafort

  2. School of Human Sciences, The University of Western Australia, Perth, WA, Australia

    Colette Moses & Pilar Blancafort

  3. School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia

    Mahira Arooj

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  4. Pilar Blancafort
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Correspondence to Pilar Blancafort .

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Editors and Affiliations

  1. Department of Biochemistry, Institute of Biochemistry and Technical Biochemistry, Stuttgart, Germany

    Albert Jeltsch

  2. Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Marianne G. Rots

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Waryah, C.B., Moses, C., Arooj, M., Blancafort, P. (2018). Zinc Fingers, TALEs, and CRISPR Systems: A Comparison of Tools for Epigenome Editing. In: Jeltsch, A., Rots, M. (eds) Epigenome Editing. Methods in Molecular Biology, vol 1767. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7774-1_2

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  • DOI: https://doi.org/10.1007/978-1-4939-7774-1_2

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7773-4

  • Online ISBN: 978-1-4939-7774-1

  • eBook Packages: Springer Protocols

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