Evidence map›Paper›PMID 35234927›Full record

ArticleNucleic acids research2022

Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing.

Henriette O'Geen, Marketa Tomkova, Jacquelyn A Combs, Emma K Tilley, David J Segal

Abstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
–field-weighted citation impact
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

52 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026
    Review
  15. Article
  16. Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  17. International journal of biological sciences · 2026
    Review
  18. Review
  19. Article
  20. Review
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

5 authors.

Henriette O'GeenGenome Center, University of California, Davis, CA 95616, USA.ORCID 0000-0002-5569-7971
Marketa TomkovaGenome Center, University of California, Davis, CA 95616, USA.
Jacquelyn A CombsGenome Center, University of California, Davis, CA 95616, USA.
Emma K TilleyGenome Center, University of California, Davis, CA 95616, USA.
David J SegalGenome Center, University of California, Davis, CA 95616, USA.ORCID 0000-0001-8962-3105

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Gina M Dayton · 2002 to 2026
$84.9M
UC Davis Shared Astrios Cell SorterS10OD018223 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SHACKLETT, BARBARA L. · 2015 to 2015
$555k
Determinants of Persistence in Epigenetic EditingR21HG010559 · NHGRI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SEGAL, DAVID J · 2019 to 2020
$415k
NCI NIH HHS P30 CA093373NHGRI NIH HHS R21 HG010559NIH HHS S10 OD018223
6 · The paper itself

Abstract

Precision epigenome editing has gained significant attention as a method to modulate gene expression without altering genetic information. However, a major limiting factor has been that the gene expression changes are often transient, unlike the life-long epigenetic changes that occur frequently in nature. Here, we systematically interrogate the ability of CRISPR/dCas9-based epigenome editors (Epi-dCas9) to engineer persistent epigenetic silencing. We elucidated cis regulatory features that contribute to the differential stability of epigenetic reprogramming, such as the active transcription histone marks H3K36me3 and H3K27ac strongly correlating with resistance to short-term repression and resistance to long-term silencing, respectively. H3K27ac inversely correlates with increased DNA methylation. Interestingly, the dependance on H3K27ac was only observed when a combination of KRAB-dCas9 and targetable DNA methyltransferases (DNMT3A-dCas9 + DNMT3L) was used, but not when KRAB was replaced with the targetable H3K27 histone methyltransferase Ezh2. In addition, programmable Ezh2/DNMT3A + L treatment demonstrated enhanced engineering of localized DNA methylation and was not sensitive to a divergent chromatin state. Our results highlight the importance of local chromatin features for heritability of programmable silencing and the differential response to KRAB- and Ezh2-based epigenetic editing platforms. The information gained in this study provides fundamental insights into understanding contextual cues to more predictably engineer persistent silencing.

Indexed as

EpigenomeGene EditingChromatinCRISPR-Cas SystemsDNA MethylationEpigenesis, GeneticGene SilencingChromatin

Identifiers

PMID35234927
PMCPMC8989539

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Registered trials

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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.