Evidence map›Paper›PMID 25849900›Full record

ArticleNature biotechnology2015

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

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

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,012 papers.

0numbers the graph read from it
0cells of the map it votes in
1,012citing papers in PubMed
100.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1,012 citing papers in PubMed, 1,839 citations in OpenAlex.

  1. Review
  2. Role of Chromatin-Associated RNAs in Eye Physiology and Pathology.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  3. CRISPR/Cas Systems: Biological Basis and Genome Editing Applications.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
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952 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Isaac B Hilton1] Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA. [2] Center for Genomic &Computational Biology, Duke University, Durham, North Carolina, USA.ORCID 0000000230648532
Anthony M D'Ippolito1] Center for Genomic &Computational Biology, Duke University, Durham, North Carolina, USA. [2] University Program in Genetics and Genomics, Duke University Medical Center, Durham, North Carolina, USA.
Christopher M Vockley1] Center for Genomic &Computational Biology, Duke University, Durham, North Carolina, USA. [2] Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA.
Pratiksha I Thakore1] Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA. [2] Center for Genomic &Computational Biology, Duke University, Durham, North Carolina, USA.
Gregory E Crawford1] Center for Genomic &Computational Biology, Duke University, Durham, North Carolina, USA. [2] Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina, USA.
Timothy E Reddy1] Center for Genomic &Computational Biology, Duke University, Durham, North Carolina, USA. [2] Department of Biostatistics &Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA.ORCID 000000027629061X
Charles A Gersbach1] Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA. [2] Center for Genomic &Computational Biology, Duke University, Durham, North Carolina, USA. [3] Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Duke University · US

Funding

Training Program in Developmental & Stem Cell BiologyT32HD040372 · NICHD · DUKE UNIVERSITY · PI Terry H Lechler · 2001 to 2026
$8.9M
Genetics Training Grant-Year 26T32GM007754 · NIGMS · DUKE UNIVERSITY · PI HAASE, STEVEN B · 1985 to 2019
$8.3M
Decoding and Reprogramming the Corticosteroid Transcriptional Regulatory NetworkU01HG007900 · NHGRI · DUKE UNIVERSITY · PI REDDY, TIMOTHY E · 2015 to 2017
$5.9M
Engineering Targeted Epigenetic Modifiers for Precise Control of Gene RegulationR01DA036865 · NIDA · DUKE UNIVERSITY · PI CRAWFORD, GREGORY E, GERSBACH, CHARLES A. · 2013 to 2017
$2.6M
Engineering Morphogenetic Factors for Enhanced Genetic ReprogrammingDP2OD008586 · OD · DUKE UNIVERSITY · PI GERSBACH, CHARLES A. · 2011 to 2011
$2.4M
Tissue Procurement and Analysis CoreP30AR066527 · NIAMS · DUKE UNIVERSITY · PI SELIM, MARIA ANGELICA · 2014 to 2015
$1.3M
NHGRI NIH HHS U01 HG007900NHGRI NIH HHS U01HG007900NIAMS NIH HHS P30 AR066527NIAMS NIH HHS P30AR066527NICHD NIH HHS T32 HD040372NIDA NIH HHS R01 DA036865NIDA NIH HHS R01DA036865NIGMS NIH HHS T32 GM007754NIH HHS DP2 OD008586NIH HHS DP2OD008586
6 · The paper itself

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.

Indexed as

Enhancer Elements, GeneticAcetyltransferasesCRISPR-Cas SystemsE1A-Associated p300 ProteinEpigenomicsHEK293 CellsHumansPromoter Regions, GeneticRNA EditingRNA, Guide, CRISPR-Cas SystemsTranscriptional ActivationAcetyltransferasesE1A-Associated p300 ProteinEP300 protein, humanRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID25849900
PMCPMC4430400
OpenAlexW2066783444

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.