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Locus-specific histone deacetylation using a synthetic CRISPR-Cas9-based HDAC

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  • Deborah Y. Kwon

    (University of Pennsylvania School of Medicine)

  • Ying-Tao Zhao

    (University of Pennsylvania School of Medicine)

  • Janine M. Lamonica

    (University of Pennsylvania School of Medicine)

  • Zhaolan Zhou

    (University of Pennsylvania School of Medicine)

Abstract

Efforts to manipulate locus-specific histone acetylation to assess their causal role in gene expression and cellular and behavioural phenotypes have been impeded by a lack of experimental tools. The Cas9 nuclease has been adapted to target epigenomic modifications, but a detailed description of the parameters of such synthetic epigenome remodellers is still lacking. Here we describe a Cas9-based histone deacetylase (HDAC) and the design principles required to achieve locus-specific histone deacetylation. We assess its range of activity and specificity, and analyse target gene expression in two different cell types to investigate cellular context-dependent effects. Our findings demonstrate that the chromatin environment is an important element to consider when utilizing this synthetic HDAC.

Suggested Citation

  • Deborah Y. Kwon & Ying-Tao Zhao & Janine M. Lamonica & Zhaolan Zhou, 2017. "Locus-specific histone deacetylation using a synthetic CRISPR-Cas9-based HDAC," Nature Communications, Nature, vol. 8(1), pages 1-8, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15315
    DOI: 10.1038/ncomms15315
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