ArticleGenome research2018
A modular dCas9-SunTag DNMT3A epigenome editing system overcomes pervasive off-target activity of direct fusion dCas9-DNMT3A constructs.
Article in Genome research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 186 citations in OpenAlex.
- Tuning epigenetics to enhance cancer virotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Transgene-free genome editing in plants.aBIOTECH · 2026Review
- Programmable aging function-related mitochondrial DNA 5-methylcytosine (m5C) modification with a TALE-directed methyltransferase.Cell communication and signaling : CCS · 2026Article
- Glucocorticoid Receptor Signaling: Multilevel Organization, Roles in Fetal Development, and Postnatal Outcomes.International journal of molecular sciences · 2026Review
- Review
- Comprehensive profiling of CRISPR/dCas9 epigenome editors indicates a complex link between on and off target effects.Genome biology · 2026Article
- High-throughputbioRxiv : the preprint server for biology · 2025Article
- Exploring CRISPR-Cas: The transformative impact of gene editing in molecular biology.Molecular therapy. Nucleic acids · 2025Review
- Versatile molecular tools enabling customizable DNA methylation editing in Arabidopsis.Nature communications · 2025Article
- CRISPR targeting of H3K4me3 activates gene expression and unlocks centromere-proximal crossover recombination in Arabidopsis.Nature communications · 2025Article
- All-in-one vectors for epigenetic CRISPR inhibition ofMolecular therapy. Methods & clinical development · 2025Article
- Programmable genome engineering and gene modifications for plant biodesign.Plant communications · 2025Review
- Modulating immune cell fate and inflammation through CRISPR-mediated DNA methylation editing.Science advances · 2025Article
- Fertile androgenetic mice generated by targeted epigenetic editing of imprinting control regions.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CRISPR GENome and epigenome engineering improves loss-of-function genetic-screening approaches.Cell reports methods · 2025Article
- DNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities.Clinical epigenetics · 2025Review
- Dual-directional epi-genotoxicity assay for assessing chemically induced epigenetic effects utilizing the housekeeping TK gene.Scientific reports · 2025Article
- Characterization of Rationally Designed CRISPR/Cas9-Based DNA Methyltransferases with Distinct Methyltransferase and Gene Silencing Activities in Human Cell Lines and Primary Human T Cells.ACS synthetic biology · 2025Article
- The generation of novel epialleles in plants: the prospective behind re-shaping the epigenome.Frontiers in plant science · 2025Review
- DNA methylation in mammalian development and disease.Nature reviews. Genetics · 2025Review
45 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Detection of DNA methylation in the genome has been possible for decades; however, the ability to deliberately and specifically manipulate local DNA methylation states in the genome has been extremely limited. Consequently, this has impeded our understanding of the direct effect of DNA methylation on transcriptional regulation and transcription factor binding in the native chromatin context. Thus, highly specific targeted epigenome editing tools are needed to address this. Recent adaptations of genome editing technologies, including fusion of the DNMT3A DNA methyltransferase catalytic domain to catalytically inactive Cas9 (dC9-D3A), have aimed to alter DNA methylation at desired loci. Here, we show that these tools exhibit consistent off-target DNA methylation deposition in the genome, limiting their capabilities to unambiguously assess the functional consequences of DNA methylation. To address this, we developed a modular dCas9-SunTag (dC9Sun-D3A) system that can recruit multiple DNMT3A catalytic domains to a target site for editing DNA methylation. dC9Sun-D3A is tunable, specific, and exhibits much higher induction of DNA methylation at target sites than the dC9-D3A direct fusion protein. Importantly, genome-wide characterization of dC9Sun-D3A binding sites and DNA methylation revealed minimal off-target protein binding and induction of DNA methylation with dC9Sun-D3A, compared to pervasive off-target methylation by dC9-D3A. Furthermore, we used dC9Sun-D3A to demonstrate the binding sensitivity to DNA methylation for CTCF and NRF1 in situ. Overall, this modular dC9Sun-D3A system enables precise DNA methylation deposition with the lowest off-target DNA methylation levels reported to date, allowing accurate functional determination of the role of DNA methylation at single loci.
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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.