ArticleNucleic acids research2024
Chromatin context-dependent effects of epigenetic drugs on CRISPR-Cas9 editing.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- OmniEdit: A unified CRISPR/Cas9 platform for precise genome engineering and strain optimization of theSynthetic and systems biotechnology · 2026Article
- Chromatin Modifications Orchestrate DNA Repair Pathway Choice: Epigenetics Strategies for Enhancing CRISPR-Cas9-Mediated Knock-In Efficiency.Cell proliferation · 2026Review
- Dual-line Genome-scale CRISPR Screening Enables Robust Target Gene Discovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CRISPR/Cas9-Based Genome Editing: Understanding Differences in DNA Repair Pathways, Profiles, and Outcomes.International journal of molecular sciences · 2026Review
- Long-term restoration of auditory function in a DFNA2 mouse model by adenine base editing.EMBO molecular medicine · 2026Article
- A systematic guide for identifying transcription factors that directly regulate the expression of a gene of interest.Genome research · 2026Review
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Precision therapeutic tRNA rescue of nonsense mutation R166X inJournal of precision medicine (Amsterdam, Netherlands) · 2025Article
- Validation of caprine H11 and the Rosa26 platform for transgene integration via CRISPR-based system: investigations on stable transgene expression and genetic biosafety.Functional & integrative genomics · 2025Article
- DeepIndel: An Interpretable Deep Learning Approach for Predicting CRISPR/Cas9-Mediated Editing Outcomes.International journal of molecular sciences · 2024Article
- Widespread chromatin context-dependencies of DNA double-strand break repair proteins.Nature communications · 2024Article
- Making gene editing accessible in resource limited environments: recommendations to guide a first-time user.Frontiers in genome editing · 2024Review
- Mechanisms and technologies in cancer epigenetics.Frontiers in oncology · 2024Review
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Authors and funding
11 authors.
Funding
Abstract
The efficiency and outcome of CRISPR/Cas9 editing depends on the chromatin state at the cut site. It has been shown that changing the chromatin state can influence both the efficiency and repair outcome, and epigenetic drugs have been used to improve Cas9 editing. However, because the target proteins of these drugs are not homogeneously distributed across the genome, the efficacy of these drugs may be expected to vary from locus to locus. Here, we systematically analyzed this chromatin context-dependency for 160 epigenetic drugs. We used a human cell line with 19 stably integrated reporters to induce a double-stranded break in different chromatin environments. We then measured Cas9 editing efficiency and repair pathway usage by sequencing the mutational signatures. We identified 58 drugs that modulate Cas9 editing efficiency and/or repair outcome dependent on the local chromatin environment. For example, we find a subset of histone deacetylase inhibitors that improve Cas9 editing efficiency throughout all types of heterochromatin (e.g. PCI-24781), while others were only effective in euchromatin and H3K27me3-marked regions (e.g. apicidin). In summary, this study reveals that most epigenetic drugs alter CRISPR editing in a chromatin-dependent manner, and provides a resource to improve Cas9 editing more selectively at the desired location.
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