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CRISPR-Cas9 has been utilized, through the fusion of catalytic dead nuclease with chromatin-remodellers, to modify the epigenetic state of specific loci.
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Here the authors describe a Cas9-based histone deacetylase (HDAC) and the design principles required to achieve locus-specific histone deacetylation. They assess its range of activity and specificity, and analyse target gene expression in two different cell types to investigate cellular context-dependent effects. Their findings demonstrate that the chromatin environment is an important element to consider when utilizing this synthetic HDAC.