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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hilton, IB; D'Ippolito, AM; Vockley, CM; Thakore, PI; Crawford, GE; Reddy, TE; Gersbach, CA

Published Date

  • May 2015

Published In

Volume / Issue

  • 33 / 5

Start / End Page

  • 510 - 517

PubMed ID

  • 25849900

Electronic International Standard Serial Number (EISSN)

  • 1546-1696

International Standard Serial Number (ISSN)

  • 1087-0156

Digital Object Identifier (DOI)

  • 10.1038/nbt.3199

Language

  • eng