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Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Locus-specific histone deacetylation using a synthetic CRISPR-Cas9-based HDAC.
Nature Communications 2017 May 13
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.
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