Review Article | Published:

Editing the epigenome: technologies for programmable transcription and epigenetic modulation

Nature Methods volume 13, pages 127137 (2016) | Download Citation

Abstract

Gene regulation is a complex and tightly controlled process that defines cell identity, health and disease, and response to pharmacologic and environmental signals. Recently developed DNA-targeting platforms, including zinc finger proteins, transcription activator-like effectors (TALEs) and the clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 system, have enabled the recruitment of transcriptional modulators and epigenome-modifying factors to any genomic site, leading to new insights into the function of epigenetic marks in gene expression. Additionally, custom transcriptional and epigenetic regulation is facilitating refined control over cell function and decision making. The unique properties of the CRISPR-Cas9 system have created new opportunities for high-throughput genetic screens and multiplexing targets to manipulate complex gene expression patterns. This Review summarizes recent technological developments in this area and their application to biomedical challenges. We also discuss remaining limitations and necessary future directions for this field.

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Acknowledgements

This work was supported by US National Institutes of Health (NIH) grants R01DA036865, U01HG007900, R21AR065956 and P30AR066527; an NIH Director's New Innovator Award (DP2OD008586); and a US National Science Foundation (NSF) Faculty Early Career Development (CAREER) award (CBET-1151035) to C.A.G. P.I.T. was supported by an NSF Graduate Research Fellowship and an American Heart Association Mid-Atlantic Affiliate Predoctoral Fellowship. J.B.B. was supported by an NIH biotechnology training grant (T32GM008555).

Author information

Affiliations

  1. Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.

    • Pratiksha I Thakore
    • , Joshua B Black
    • , Isaac B Hilton
    •  & Charles A Gersbach
  2. Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, USA.

    • Pratiksha I Thakore
    • , Joshua B Black
    • , Isaac B Hilton
    •  & Charles A Gersbach
  3. Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, USA.

    • Charles A Gersbach

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Competing interests

The authors are inventors on patent applications related to genome engineering (WO 2014/197748). C.A.G. is a scientific advisor to Editas Medicine, a company engaged in therapeutic development of genome engineering technologies.

Corresponding author

Correspondence to Charles A Gersbach.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nmeth.3733

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