Evidence map›Paper›PMID 26501517›Full record

ArticleNature methods2015

Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements.

Pratiksha I Thakore, Anthony M D'Ippolito, Lingyun Song, Alexias Safi, Nishkala K Shivakumar, Ami M Kabadi, Timothy E Reddy, Gregory E Crawford, Charles A Gersbach

Abstract read
In one paragraph

Article in Nature methods, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 615 papers.

0numbers the graph read from it
0cells of the map it votes in
615citing papers in PubMed
36.8field-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

615 citing papers in PubMed, 1,028 citations in OpenAlex.

  1. Role of Chromatin-Associated RNAs in Eye Physiology and Pathology.Methods in molecular biology (Clifton, N.J.) · 2027
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  15. Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026
    Review
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555 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Pratiksha I ThakoreDepartment of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
Anthony M D'IppolitoCenter for Genomic and Computational Biology, Duke University, Durham, North Carolina, USA.
Lingyun SongCenter for Genomic and Computational Biology, Duke University, Durham, North Carolina, USA.
Alexias SafiCenter for Genomic and Computational Biology, Duke University, Durham, North Carolina, USA.
Nishkala K ShivakumarDepartment of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
Ami M KabadiDepartment of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
Timothy E ReddyCenter for Genomic and Computational Biology, Duke University, Durham, North Carolina, USA.
Gregory E CrawfordCenter for Genomic and Computational Biology, Duke University, Durham, North Carolina, USA.
Charles A GersbachDepartment of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
Duke University · USDuke Medical Center · US

Funding

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 HALL, RUSSELL P. · 2014 to 2015
$1.3M
Genome Editing of Stem Cells for Analysis of Osteoarthritis Causal VariantsR21AR065956 · NIAMS · DUKE UNIVERSITY · PI GERSBACH, CHARLES A., GUILAK, FARSHID · 2014 to 2015
$382k
NHGRI NIH HHS U01 HG007900NHGRI NIH HHS U01HG007900NIAMS NIH HHS P30 AR066527NIAMS NIH HHS P30AR066527NIAMS NIH HHS R21 AR065956NIAMS NIH HHS R21AR065956NIDA NIH HHS R01 DA036865NIDA NIH HHS R01DA036865NIGMS NIH HHS T32 GM007754NIH HHS DP2 OD008586NIH HHS DP2OD008586
6 · The paper itself

Abstract

Epigenome editing with the CRISPR (clustered, regularly interspaced, short palindromic repeats)-Cas9 platform is a promising technology for modulating gene expression to direct cell phenotype and to dissect the causal epigenetic mechanisms of gene regulation. Fusions of nuclease-inactive dCas9 to the Krüppel-associated box (KRAB) repressor (dCas9-KRAB) can silence target gene expression, but the genome-wide specificity and the extent of heterochromatin formation catalyzed by dCas9-KRAB are not known. We targeted dCas9-KRAB to the HS2 enhancer, a distal regulatory element that orchestrates the expression of multiple globin genes, and observed highly specific induction of H3K9 trimethylation (H3K9me3) at the enhancer and decreased chromatin accessibility of both the enhancer and its promoter targets. Targeted epigenetic modification of HS2 silenced the expression of multiple globin genes, with minimal off-target changes in global gene expression. These results demonstrate that repression mediated by dCas9-KRAB is sufficiently specific to disrupt the activity of individual enhancers via local modification of the epigenome.

Indexed as

Epigenesis, GeneticClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated ProteinsCRISPR-Cas SystemsEnhancer Elements, GeneticEpigenomicsGene Expression Regulation, ViralGlobinsHEK293 CellsHumansK562 CellsLentivirusRegulatory Elements, TranscriptionalRepressor ProteinsRNA, Guide, CRISPR-Cas SystemsViral ProteinsCRISPR-Associated ProteinsGlobinsRepressor ProteinsRNA, Guide, CRISPR-Cas SystemsViral Proteins

Identifiers

PMID26501517
PMCPMC4666778
OpenAlexW2239511084

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.