Evidence map›Paper›PMID 38608704›Full record

ArticleCell2024

Chromatin context-dependent regulation and epigenetic manipulation of prime editing.

Xiaoyi Li, Wei Chen, Beth K Martin, Diego Calderon, Choli Lee, Junhong Choi, Florence M Chardon, Troy A McDiarmid, Riza M Daza, Haedong Kim and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
12.4field-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

68 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. bioRxiv : the preprint server for biology · 2026
    Article
  7. Article
  8. A primer on prime: A prime editing update from advances to first-in-human trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  9. Gigabase-scale deletion scanning of the human genome.bioRxiv : the preprint server for biology · 2026
    Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026
    Review
  16. Evolution of Prime Editing: Enhancing Efficiency and Expanding Capacity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  17. Regenerative base editing enables deep lineage recording.bioRxiv : the preprint server for biology · 2026
    Article
  18. Review
  19. Review
  20. Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Xiaoyi LiDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address: xyli10@uw.edu.
Wei ChenDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Molecular Engineering and Sciences Institute, University of Washington, Seattle, WA 98195, USA.
Beth K MartinDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Diego CalderonDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Choli LeeDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Junhong ChoiDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA.
Florence M ChardonDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Troy A McDiarmidDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Riza M DazaDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Haedong KimDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Jean-Benoît LalanneDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Jenny F NathansDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA.
David S LeeDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Jay ShendureDepartment of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA 98195, USA; Allen Discovery Center for Cell Lineage Tracing, Seattle, WA 98109, USA; Seattle Hub for Synthetic Biology, Seattle, WA 98109, USA. Electronic address: shendure@uw.edu.
University of Washington · USHoward Hughes Medical Institute · US

Funding

Massively parallel characterization of variants and elements impacting transcriptional regulation in dynamic cellular systemsUM1HG011966 · NHGRI · UNIVERSITY OF WASHINGTON · PI Nadav Ahituv, Jay Ashok Shendure · 2021 to 2026
$9.7M
Versatile, exponentially scalable methods for single cell molecular profilingR01HG010632 · NHGRI · UNIVERSITY OF WASHINGTON · PI Jay Ashok Shendure, Bruce Colston Trapnell · 2019 to 2026
$5.9M
Molecular recording to understand the determinants of cell fate transitions in early developmentK99HG012973 · NHGRI · UNIVERSITY OF WASHINGTON · PI CHOI, JUNHONG · 2023 to 2023
$114k
Characterizing the comprehensive gene regulatory basis of autoimmunity.F32HG011817 · NHGRI · UNIVERSITY OF WASHINGTON · PI CALDERON, DIEGO · 2021 to 2021
$64k
NHGRI NIH HHS F32 HG011817NHGRI NIH HHS K99 HG012973NHGRI NIH HHS R01 HG010632NHGRI NIH HHS UM1 HG011966
6 · The paper itself

Abstract

We set out to exhaustively characterize the impact of the cis-chromatin environment on prime editing, a precise genome engineering tool. Using a highly sensitive method for mapping the genomic locations of randomly integrated reporters, we discover massive position effects, exemplified by editing efficiencies ranging from ∼0% to 94% for an identical target site and edit. Position effects on prime editing efficiency are well predicted by chromatin marks, e.g., positively by H3K79me2 and negatively by H3K9me3. Next, we developed a multiplex perturbational framework to assess the interaction of trans-acting factors with the cis-chromatin environment on editing outcomes. Applying this framework to DNA repair factors, we identify HLTF as a context-dependent repressor of prime editing. Finally, several lines of evidence suggest that active transcriptional elongation enhances prime editing. Consistent with this, we show we can robustly decrease or increase the efficiency of prime editing by preceding it with CRISPR-mediated silencing or activation, respectively.

Indexed as

ChromatinCRISPR-Cas SystemsEpigenesis, GeneticGene EditingHistone CodeHistonesHumansTranscription FactorsChromatinHistonesTranscription Factorscis-chromatin effectcis x trans interactionsDNA damage repairepigenome editinggenome engineeringprime editing

Identifiers

PMID38608704
PMCPMC11088515
OpenAlexW4394727560

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.