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

Deborah Y. Kwon, Ying-Tao Zhao, Janine M. Lamonica and Zhaolan Zhou ()
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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

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15315

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