Evidence map›Paper›PMID 27899645›Full record

ArticleNucleic acids research2017

Efficient targeted DNA methylation with chimeric dCas9-Dnmt3a-Dnmt3L methyltransferase.

Peter Stepper, Goran Kungulovski, Renata Z Jurkowska, Tamir Chandra, Felix Krueger, Richard Reinhardt, Wolf Reik, Albert Jeltsch, Tomasz P Jurkowski

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers.

0numbers the graph read from it
0cells of the map it votes in
182citing papers in PubMed
16.2field-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

182 citing papers in PubMed, 316 citations in OpenAlex.

  1. Review
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  8. Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026
    Review
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  19. Designing nucleic acid-based therapeutics for cancer treatment: Updates on the state of the art.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  20. Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review

122 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 3 institutions in 2 countries.

Peter StepperInstitute of Biochemistry, Pfaffenwaldring 55, Faculty of Chemistry, University of Stuttgart, D-70569 Stuttgart, Germany.
Goran KungulovskiInstitute of Biochemistry, Pfaffenwaldring 55, Faculty of Chemistry, University of Stuttgart, D-70569 Stuttgart, Germany.
Renata Z JurkowskaInstitute of Biochemistry, Pfaffenwaldring 55, Faculty of Chemistry, University of Stuttgart, D-70569 Stuttgart, Germany.
Tamir ChandraEpigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK; The Welcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
Felix KruegerThe Babraham Institute, Cambridge CB22 3AT, UK.
Richard ReinhardtMax Planck Genome-Centre Cologne, Carl-von-Linné-Weg 10, D-50829 Cologne, Germany.
Wolf ReikEpigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK; The Welcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
Albert JeltschInstitute of Biochemistry, Pfaffenwaldring 55, Faculty of Chemistry, University of Stuttgart, D-70569 Stuttgart, Germany.
Tomasz P JurkowskiInstitute of Biochemistry, Pfaffenwaldring 55, Faculty of Chemistry, University of Stuttgart, D-70569 Stuttgart, Germany.
University of Stuttgart · DEBabraham Institute · GBMax Planck Institute for Plant Breeding Research · DE

Funding

PILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROBERT S. SANDLER · 1985 to 2026
$30.5M
NIDDK NIH HHS P30 DK034987
6 · The paper itself

Abstract

DNA methylation plays a critical role in the regulation and maintenance of cell-type specific transcriptional programs. Targeted epigenome editing is an emerging technology to specifically regulate cellular gene expression in order to modulate cell phenotypes or dissect the epigenetic mechanisms involved in their control. In this work, we employed a DNA methyltransferase Dnmt3a-Dnmt3L construct fused to the nuclease-inactivated dCas9 programmable targeting domain to introduce DNA methylation into the human genome specifically at the EpCAM, CXCR4 and TFRC gene promoters. We show that targeting of these loci with single gRNAs leads to efficient and widespread methylation of the promoters. Multiplexing of several guide RNAs does not increase the efficiency of methylation. Peaks of targeted methylation were observed around 25 bp upstream and 40 bp downstream of the PAM site, while 20-30 bp of the binding site itself are protected against methylation. Potent methylation is dependent on the multimerization of Dnmt3a/Dnmt3L complexes on the DNA. Furthermore, the introduced methylation causes transcriptional repression of the targeted genes. These new programmable epigenetic editors allow unprecedented control of the DNA methylation status in cells and will lead to further advances in the understanding of epigenetic signaling.

Indexed as

DNA MethylationAnimalsCell Line, TumorCluster AnalysisCpG IslandsDNADNA (Cytosine-5-)-MethyltransferasesEndonucleasesEpigenesis, GeneticEpigenomicsGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansMiceModels, BiologicalPromoter Regions, GeneticDNADNA (Cytosine-5-)-MethyltransferasesEndonucleasesRecombinant Fusion Proteins

Identifiers

PMID27899645
PMCPMC5389507
OpenAlexW2558046424

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.