Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-05

AUTHORS

Isaac B Hilton, Anthony M D'Ippolito, Christopher M Vockley, Pratiksha I Thakore, Gregory E Crawford, Timothy E Reddy, Charles A Gersbach

ABSTRACT

Technologies that enable targeted manipulation of epigenetic marks could be used to precisely control cell phenotype or interrogate the relationship between the epigenome and transcriptional control. Here we describe a programmable, CRISPR-Cas9-based acetyltransferase consisting of the nuclease-null dCas9 protein fused to the catalytic core of the human acetyltransferase p300. The fusion protein catalyzes acetylation of histone H3 lysine 27 at its target sites, leading to robust transcriptional activation of target genes from promoters and both proximal and distal enhancers. Gene activation by the targeted acetyltransferase was highly specific across the genome. In contrast to previous dCas9-based activators, the acetyltransferase activates genes from enhancer regions and with an individual guide RNA. We also show that the core p300 domain can be fused to other programmable DNA-binding proteins. These results support targeted acetylation as a causal mechanism of transactivation and provide a robust tool for manipulating gene regulation. More... »

PAGES

510-517

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nbt.3199

    DOI

    http://dx.doi.org/10.1038/nbt.3199

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1031267114

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25849900


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