ArticlePloS one2012
Targeted DNA methylation using an artificially bisected M.HhaI fused to zinc fingers.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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.
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.
Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Reshaping the Landscape of the Genome: Toolkits for Precise DNA Methylation Manipulation and Beyond.JACS Au · 2024Review
- Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Transgenerational Epigenetic DNA Methylation Editing and Human Disease.Biomolecules · 2023Review
- Review
- Lowering DNA binding affinity of SssI DNA methyltransferase does not enhance the specificity of targeted DNA methylation in E. coli.Scientific reports · 2021Article
- Programmable protein circuit design.Cell · 2021Review
- Conditional Recruitment to a DNA-Bound CRISPR-Cas Complex Using a Colocalization-Dependent Protein Switch.ACS synthetic biology · 2020Article
- Article
- Article
- Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Targeted DNA methylation in human cells using engineered dCas9-methyltransferases.Scientific reports · 2017Article
- Targeted DNA methylation in pericentromeres with genome editing-based artificial DNA methyltransferase.PloS one · 2017Article
- Modern Genome Editing Technologies in Huntington's Disease Research.Journal of Huntington's disease · 2017Review
- Chromatin regulation at the frontier of synthetic biology.Nature reviews. Genetics · 2015Review
- Strategies for precision modulation of gene expression by epigenome editing: an overview.Epigenetics & chromatin · 2015Review
- Synthetic epigenetics-towards intelligent control of epigenetic states and cell identity.Clinical epigenetics · 2015Article
- Epigenetic mechanisms underlying the pathogenesis of neurogenetic diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2014Review
- Deep sequencing of large library selections allows computational discovery of diverse sets of zinc fingers that bind common targets.Nucleic acids research · 2014Article
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- Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Little is known about the effects of single DNA methylation events on gene transcription. The ability to direct the methylation toward a single unique site within a genome would have broad use as a tool to study the effects of specific epigenetic changes on transcription. A targeted enzyme might also be useful in a therapy for diseases with an epigenetic component or as a means to site-specifically label DNA. Previous studies have sought to target methyltransferase activity by fusing DNA binding proteins to methyltransferases. However, the methyltransferase domain remains active even when the DNA binding protein is unbound, resulting in significant off-target methylation. A better strategy would make methyltransferase activity contingent upon the DNA binding protein's association with its DNA binding site. We have designed targeted methyltransferases by fusing zinc fingers to the fragments of artificially-bisected, assembly-compromised methyltransferases. The zinc fingers' binding sites flank the desired target site for methylation. Zinc finger binding localizes the two fragments near each other encouraging their assembly only over the desired site. Through a combination of molecular modeling and experimental optimization in E. coli, we created an engineered methyltransferase derived from M.HhaI with 50-60% methylation at a target site and nearly undetectable levels of methylation at a non-target M.HhaI site (1.4 ± 2.4%). Using a restriction digestion assay, we demonstrate that localization of both fragments synergistically increases methylation at the target site, illustrating the promise of our approach.
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Identifiers
What OpenQuestion holds
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.