Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers.

TitleEpigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers.
Publication TypeJournal Article
Year of Publication2015
AuthorsHilton, IB, D'Ippolito, AM, Vockley, CM, Thakore, PI, Crawford, GE, Reddy, TE, and Gersbach, CA
JournalNature Biotechnology
Volume33
Issue5
Start Page510
Pagination510 - 517
Date Published05/2015
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.

DOI10.1038/nbt.3199
Short TitleNature Biotechnology