ArticleNucleic acids research2022
Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing.
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.
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Who cites it
52 citing papers in PubMed.
- Beyond Precision: A Multidimensional Framework for Selecting Genetic Medicine Platforms.Cells · 2026Review
- From epigenetic mark detection to rational design of epigenetic editing strategies.Molecular therapy. Advances · 2026Review
- Design of optimized epigenetic regulators for durable gene silencing with application to PCSK9 in nonhuman primates.Nature biotechnology · 2026Article
- Single-cell chromatin state transitions during epigenetic memory formation.Science advances · 2026Article
- Beyond Permanent Genome Editing: Molecular Delivery Strategies for RNA Editing and Epigenome-Editing Therapeutics.International journal of molecular sciences · 2026Review
- Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026Review
- Transcriptional interference drives intronic polyadenylation at the endogenous H13/Mcts2 locus.Nucleic acids research · 2026Article
- Epigenetic editing balances TCR suppression and persistence in CAR T cells.Molecular therapy. Advances · 2026Article
- CRISPR/Cas‑based epigenome editing for osteogenic lineage commitment.Cell and tissue research · 2026Review
- Next generation technologies for CRISPR-based epigenome and transcriptional modulation.Current opinion in biomedical engineering · 2026Article
- A Functionally Conserved Enhancer is Critical for PGC1A Expression and Thermogenesis in Brown Fat.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Article
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Comprehensive profiling of CRISPR/dCas9 epigenome editors indicates a complex link between on and off target effects.Genome biology · 2026Article
- Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Review
- Exploring CRISPR-Cas: The transformative impact of gene editing in molecular biology.Molecular therapy. Nucleic acids · 2025Review
- The myoblast methylome: multiple types of associations with chromatin and transcription.Epigenetics · 2025Article
- Mechanotransduction-Epigenetic Coupling in Pulmonary Regeneration: Multifunctional Bioscaffolds as Emerging Tools.Pharmaceuticals (Basel, Switzerland) · 2025Review
Corrections and comments
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Authors and funding
5 authors.
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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.
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Registered trials
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.