Evidence map›Paper›PMID 29133799›Full record

ArticleNature communications2017

Hit-and-run epigenetic editing prevents senescence entry in primary breast cells from healthy donors.

Emily A Saunderson, Peter Stepper, Jennifer J Gomm, Lily Hoa, Adrienne Morgan, Michael D Allen, J Louise Jones, John G Gribben, Tomasz P Jurkowski, Gabriella Ficz

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

66 citing papers in PubMed, 114 citations in OpenAlex.

  1. Review
  2. Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Epigenetic networks coordinate DNA methylation across the genome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  7. Article
  8. CRISPR Technology and Its Emerging Applications.Genomics, proteomics & bioinformatics · 2025
    Review
  9. Article
  10. Article
  11. Therapeutic targeting of senescent cells in the CNS.Nature reviews. Drug discovery · 2024
    Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. CRISPR/dCas9 DNA methylation editing is heritable during human hematopoiesis and shapes immune progeny.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article

6 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

10 authors at 2 institutions in 2 countries.

Emily A SaundersonBarts Cancer Institute, John Vane Science Centre, Charterhouse Square, Queen Mary University of London, London, EC1M 6BQ, UK.ORCID http://orcid.org/0000-0003-2132-7785
Peter StepperInstitute for Biochemistry and Technical Biochemistry, Department of Biochemistry, Faculty of Chemistry, University of Stuttgart, D-70569, Stuttgart, Germany.
Jennifer J GommBarts Cancer Institute, John Vane Science Centre, Charterhouse Square, Queen Mary University of London, London, EC1M 6BQ, UK.
Lily HoaBarts Cancer Institute, John Vane Science Centre, Charterhouse Square, Queen Mary University of London, London, EC1M 6BQ, UK.ORCID http://orcid.org/0000-0002-6336-2063
Adrienne MorganBarts Cancer Institute, John Vane Science Centre, Charterhouse Square, Queen Mary University of London, London, EC1M 6BQ, UK.
Michael D AllenBarts Cancer Institute, John Vane Science Centre, Charterhouse Square, Queen Mary University of London, London, EC1M 6BQ, UK.ORCID http://orcid.org/0000-0003-2121-8087
J Louise JonesBarts Cancer Institute, John Vane Science Centre, Charterhouse Square, Queen Mary University of London, London, EC1M 6BQ, UK.
John G GribbenBarts Cancer Institute, John Vane Science Centre, Charterhouse Square, Queen Mary University of London, London, EC1M 6BQ, UK.
Tomasz P JurkowskiInstitute for Biochemistry and Technical Biochemistry, Department of Biochemistry, Faculty of Chemistry, University of Stuttgart, D-70569, Stuttgart, Germany. tomasz.jurkowski@ibc.uni-stuttgart.de.ORCID http://orcid.org/0000-0002-2012-0240
Gabriella FiczBarts Cancer Institute, John Vane Science Centre, Charterhouse Square, Queen Mary University of London, London, EC1M 6BQ, UK. g.ficz@qmul.ac.uk.ORCID http://orcid.org/0000-0001-9313-9578
Queen Mary University of London · GBUniversity of Stuttgart · DE

Funding

Medical Research Council MR/M01892X/1
6 · The paper itself

Abstract

Aberrant promoter DNA hypermethylation is a hallmark of cancer; however, whether this is sufficient to drive cellular transformation is not clear. To investigate this question, we use a CRISPR-dCas9 epigenetic editing tool, where an inactive form of Cas9 is fused to DNA methyltransferase effectors. Using this system, here we show simultaneous de novo DNA methylation of genes commonly methylated in cancer, CDKN2A, RASSF1, HIC1 and PTEN in primary breast cells isolated from healthy human breast tissue. We find that promoter methylation is maintained in this system, even in the absence of the fusion construct, and this prevents cells from engaging senescence arrest. Our data show that the key driver of this phenotype is repression of CDKN2A transcript p16 where myoepithelial cells harbour cancer-like gene expression but do not exhibit anchorage-independent growth. This work demonstrates that hit-and-run epigenetic events can prevent senescence entry, which may facilitate tumour initiation.

Indexed as

BreastCells, CulturedCell Transformation, NeoplasticCellular SenescenceCRISPR-Cas SystemsCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18DNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AEpigenomicsFemaleGene EditingHumansKruppel-Like Transcription FactorsPromoter Regions, GeneticCDKN2A protein, humanCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18DNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanHIC1 protein, humanKruppel-Like Transcription FactorsPTEN PhosphohydrolasePTEN protein, humanRASSF1 protein, humanTumor Suppressor Proteins

Identifiers

PMID29133799
PMCPMC5684409
OpenAlexW2767589262

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.