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Targeted genome regulation via synthetic programmable transcriptional regulators.

Authors
  • Piatek, Agnieszka1
  • Mahfouz, Magdy M1
  • 1 a Laboratory for Genome Engineering, Center for Desert Agriculture and Division of Biological and Environmental Sciences and Engineering , King Abdullah University of Science and Technology , Thuwal , Jeddah , Saudi Arabia.
Type
Published Article
Journal
Critical reviews in biotechnology
Publication Date
June 2017
Volume
37
Issue
4
Pages
429–440
Identifiers
DOI: 10.3109/07388551.2016.1165180
PMID: 27093352
Source
Medline
Keywords
License
Unknown

Abstract

Regulation of gene transcription controls cellular functions and coordinates responses to developmental, physiological and environmental cues. Precise and efficient molecular tools are needed to characterize the functions of single and multiple genes in linear and interacting pathways in a native context. Modular DNA-binding domains from zinc fingers (ZFs) and transcriptional activator-like proteins (TALE) are amenable to bioengineering to bind DNA target sequences of interest. As a result, ZF and TALE proteins were used to develop synthetic programmable transcription factors. However, these systems are limited by the requirement to re-engineer proteins for each new target sequence. The clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR associated 9 (Cas9) genome editing tool was recently repurposed for targeted transcriptional regulation by inactivation of the nuclease activity of Cas9. Due to the facile engineering, simplicity, precision and amenability to library construction, the CRISPR/Cas9 system is poised to revolutionize the functional genomics field across diverse eukaryotic species. In this review, we discuss the development of synthetic customizable transcriptional regulators and provide insights into their current and potential applications, with special emphasis on plant systems, in characterization of gene functions, elucidation of molecular mechanisms and their biotechnological applications.

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