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Applying CRISPR–Cas9 tools to identify and characterize transcriptional enhancers

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Abstract

The development of the CRISPR–Cas9 system triggered a revolution in the field of genome engineering. Initially, the use of this system was focused on the study of protein-coding genes but, recently, a number of CRISPR–Cas9-based tools have been developed to study non-coding transcriptional regulatory elements. These technological advances offer unprecedented opportunities for elucidating the functions of enhancers in their endogenous context. Here, we discuss the application, current limitations and future development of CRISPR–Cas9 systems to identify and characterize enhancer elements in a high-throughput manner.

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Figure 1: Functional genetic screens of active enhancers using the CRISPR–Cas system.
Figure 2: High-resolution dissection of active enhancer sequences (marked by H3K4me1 and H3K27ac) by CRISPR–Cas9 tiling screens to uncover novel regulatory elements.

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  • 22 July 2016

    In the original online version of this article, the reference citation in the following sentence was incorrect: “Since it was first used in genome engineering in 2013 (Ref. 3), the CRISPR–Cas9 system and its applications have continued to improve at an unprecedented rate.” The correct reference citations are REFS 12–15; this has now been corrected in the online version of this article.

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Acknowledgements

The authors apologize to those whose work they were not able to mention or cite owing to space limitations. R.L. is a fellow of the Fundação para a Ciência e Tecnologia, Portugal (SFRH/BD/74476/2010; POPH/FSE). This work was supported by funds of enhReg ERC-AdV (ERC-2012-ADG - N°322493) and NWO (NGI 93512001/2012) to R.A.

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Correspondence to Gozde Korkmaz or Reuven Agami.

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Lopes, R., Korkmaz, G. & Agami, R. Applying CRISPR–Cas9 tools to identify and characterize transcriptional enhancers. Nat Rev Mol Cell Biol 17, 597–604 (2016). https://doi.org/10.1038/nrm.2016.79

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