Evidence map›Paper›PMID 30540740›Full record

ArticlePLoS biology2018

Heterochromatin delays CRISPR-Cas9 mutagenesis but does not influence the outcome of mutagenic DNA repair.

Eirini M Kallimasioti-Pazi, Keerthi Thelakkad Chathoth, Gillian C Taylor, Alison Meynert, Tracy Ballinger, Martijn J E Kelder, Sébastien Lalevée, Ildem Sanli, Robert Feil, Andrew J Wood

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
4.0field-weighted citation impact, top 5% 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

67 citing papers in PubMed, 97 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026
    Review
  5. Regenerative base editing enables deep lineage recording.bioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Harnessing CRISPR potential for intervertebral disc regeneration strategies.Frontiers in bioengineering and biotechnology · 2025
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Eirini M Kallimasioti-PaziMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Keerthi Thelakkad ChathothMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Gillian C TaylorMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Alison MeynertMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Tracy BallingerMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Martijn J E KelderMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Sébastien LalevéeInstitute of Molecular Genetics of Montpellier (IGMM), CNRS and University of Montpellier, Montpellier, France.
Ildem SanliInstitute of Molecular Genetics of Montpellier (IGMM), CNRS and University of Montpellier, Montpellier, France.
Robert FeilInstitute of Molecular Genetics of Montpellier (IGMM), CNRS and University of Montpellier, Montpellier, France.
Andrew J WoodMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0002-0653-2070
Western General Hospital · GBCentre National de la Recherche Scientifique · FR

Funding

Medical Research CouncilWellcome Trust 102560/Z/13/Z
6 · The paper itself

Abstract

Genome editing occurs in the context of chromatin, which is heterogeneous in structure and function across the genome. Chromatin heterogeneity is thought to affect genome editing efficiency, but this has been challenging to quantify due to the presence of confounding variables. Here, we develop a method that exploits the allele-specific chromatin status of imprinted genes in order to address this problem in cycling mouse embryonic stem cells (mESCs). Because maternal and paternal alleles of imprinted genes have identical DNA sequence and are situated in the same nucleus, allele-specific differences in the frequency and spectrum of mutations induced by CRISPR-Cas9 can be unequivocally attributed to epigenetic mechanisms. We found that heterochromatin can impede mutagenesis, but to a degree that depends on other key experimental parameters. Mutagenesis was impeded by up to 7-fold when Cas9 exposure was brief and when intracellular Cas9 expression was low. In contrast, the outcome of mutagenic DNA repair was unaffected by chromatin state, with similar efficiencies of homology-directed repair (HDR) and deletion spectra on maternal and paternal chromosomes. Combined, our data show that heterochromatin imposes a permeable barrier that influences the kinetics, but not the endpoint, of CRISPR-Cas9 genome editing and suggest that therapeutic applications involving low-level Cas9 exposure will be particularly affected by chromatin status.

Indexed as

AnimalsBase SequenceCRISPR-Cas SystemsDNA Breaks, Double-StrandedDNA RepairEndonucleasesGene EditingGenomeHeterochromatinMiceMice, Inbred C57BLMouse Embryonic Stem CellsMutagenesis, InsertionalMutagensMutationRecombinational DNA RepairEndonucleasesHeterochromatinMutagens

Identifiers

PMID30540740
PMCPMC6306241
OpenAlexW2904494529

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.