ArticleNucleic acids research2017
dCas9-based epigenome editing suggests acquisition of histone methylation is not sufficient for target gene repression.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.
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Who cites it
136 citing papers in PubMed, 250 citations in OpenAlex.
- Non-Viral CRISPR carriers: transient delivery with lasting effects.Drug delivery · 2026Review
- H4K12 Lactylation Impairs Dopaminergic Neuron Energy Metabolism via the HIF-1α/NDUFS1 Pathway in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DNA Methylation as a Programmable Information Layer: From Molecular Marks to Disease State Engineering.International journal of molecular sciences · 2026Review
- Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026Review
- CRISPR/Cas‑based epigenome editing for osteogenic lineage commitment.Cell and tissue research · 2026Review
- In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Crop biofortification for global food security: advances in genetic engineering and biotechnological approaches.Plant molecular biology · 2026Review
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- dHyperCas12a enables multiplexed CRISPRi screens.Nature communications · 2026Article
- DOT1L provides transcriptional memory through PRC1.1 antagonism.Nature cell biology · 2026Article
- Advances and challenges of precision epigenetic therapy in treating genomic imprinting diseases.Translational pediatrics · 2026Review
- Article
- Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Neurogenesis and Neuroinflammation in Dialogue: Mapping Gaps, Modulating Microglia, Rewiring Aging.Cells · 2026Review
- H3K18 lactylation potentiates microglial polarization via the TLR4 pathway in diabetes-induced cognitive impairment.JCI insight · 2025Article
- Epigenetic editing of Cartpt promotes acquisition and extinction of cocaine memory.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms and applications of epigenome editing in plants: current status, challenges and future perspectives.Functional & integrative genomics · 2025Review
- Analog epigenetic memory revealed by targeted chromatin editing.Cell genomics · 2025Article
- Reversing transgene silencing via targeted chromatin editing.bioRxiv : the preprint server for biology · 2025Article
- FTO inhibition attenuates renal fibrosis by downregulating ferroptosis activator ACSL4 and profibrotic factor TGFBI.iScience · 2025Article
76 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Distinct epigenomic profiles of histone marks have been associated with gene expression, but questions regarding the causal relationship remain. Here we investigated the activity of a broad collection of genomically targeted epigenetic regulators that could write epigenetic marks associated with a repressed chromatin state (G9A, SUV39H1, Krüppel-associated box (KRAB), DNMT3A as well as the first targetable versions of Ezh2 and Friend of GATA-1 (FOG1)). dCas9 fusions produced target gene repression over a range of 0- to 10-fold that varied by locus and cell type. dCpf1 fusions were unable to repress gene expression. The most persistent gene repression required the action of several effector domains; however, KRAB-dCas9 did not contribute to persistence in contrast to previous reports. A 'direct tethering' strategy attaching the Ezh2 methyltransferase enzyme to dCas9, as well as a 'recruitment' strategy attaching the N-terminal 45 residues of FOG1 to dCas9 to recruit the endogenous nucleosome remodeling and deacetylase complex, were both successful in targeted deposition of H3K27me3. Surprisingly, however, repression was not correlated with deposition of either H3K9me3 or H3K27me3. Our results suggest that so-called repressive histone modifications are not sufficient for gene repression. The easily programmable dCas9 toolkit allowed precise control of epigenetic information and dissection of the relationship between the epigenome and gene regulation.
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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.