Zinc fingers, TALEs, and CRISPR systems: A comparison of tools for epigenome editing

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

Research output: Chapter in Book/Conference paperChapter

23 Citations (Scopus)

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.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
EditorsAlbert Jeltsch, Marianne G. Rots
Place of PublicationUSA
PublisherHumana Press
Pages19-63
Number of pages45
ISBN (Electronic)9781493977741
ISBN (Print)9781493977734
DOIs
Publication statusPublished - 10 Mar 2018

Publication series

NameMethods in Molecular Biology
Volume1767
ISSN (Print)1064-3745

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  • Cite this

    Waryah, C. B., Moses, C., Arooj, M., & Blancafort, P. (2018). Zinc fingers, TALEs, and CRISPR systems: A comparison of tools for epigenome editing. In A. Jeltsch, & M. G. Rots (Eds.), Methods in Molecular Biology (pp. 19-63). (Methods in Molecular Biology; Vol. 1767). Humana Press. https://doi.org/10.1007/978-1-4939-7774-1_2