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

Publication ,  Journal Article
Hilton, IB; D'Ippolito, AM; Vockley, CM; Thakore, PI; Crawford, GE; Reddy, TE; Gersbach, CA
Published in: Nat Biotechnol
May 2015

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.

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Published In

Nat Biotechnol

DOI

EISSN

1546-1696

Publication Date

May 2015

Volume

33

Issue

5

Start / End Page

510 / 517

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • RNA, Guide, CRISPR-Cas Systems
  • RNA Editing
  • Promoter Regions, Genetic
  • Humans
  • HEK293 Cells
  • Epigenomics
  • Enhancer Elements, Genetic
  • E1A-Associated p300 Protein
  • CRISPR-Cas Systems
 

Citation

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Hilton, I. B., D’Ippolito, A. M., Vockley, C. M., Thakore, P. I., Crawford, G. E., Reddy, T. E., & Gersbach, C. A. (2015). Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat Biotechnol, 33(5), 510–517. https://doi.org/10.1038/nbt.3199
Hilton, Isaac B., Anthony M. D’Ippolito, Christopher M. Vockley, Pratiksha I. Thakore, Gregory E. Crawford, Timothy E. Reddy, and Charles A. Gersbach. “Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers.Nat Biotechnol 33, no. 5 (May 2015): 510–17. https://doi.org/10.1038/nbt.3199.
Hilton IB, D’Ippolito AM, Vockley CM, Thakore PI, Crawford GE, Reddy TE, et al. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat Biotechnol. 2015 May;33(5):510–7.
Hilton, Isaac B., et al. “Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers.Nat Biotechnol, vol. 33, no. 5, May 2015, pp. 510–17. Pubmed, doi:10.1038/nbt.3199.
Hilton IB, D’Ippolito AM, Vockley CM, Thakore PI, Crawford GE, Reddy TE, Gersbach CA. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat Biotechnol. 2015 May;33(5):510–517.

Published In

Nat Biotechnol

DOI

EISSN

1546-1696

Publication Date

May 2015

Volume

33

Issue

5

Start / End Page

510 / 517

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • RNA, Guide, CRISPR-Cas Systems
  • RNA Editing
  • Promoter Regions, Genetic
  • Humans
  • HEK293 Cells
  • Epigenomics
  • Enhancer Elements, Genetic
  • E1A-Associated p300 Protein
  • CRISPR-Cas Systems