ArticleNucleic acids research2010
Heterodimeric DNA methyltransferases as a platform for creating designer zinc finger methyltransferases for targeted DNA methylation in cells.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Review
- Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.Methods in molecular biology (Clifton, N.J.) · 2024Article
- DNA methylation and de-methylation using hybrid site-targeting proteins.Genome biology · 2018Review
- Genome-wide determination of on-target and off-target characteristics for RNA-guided DNA methylation by dCas9 methyltransferases.GigaScience · 2018Article
- 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
- Modern Genome Editing Technologies in Huntington's Disease Research.Journal of Huntington's disease · 2017Review
- Induced Pluripotent Stem Cells Meet Genome Editing.Cell stem cell · 2016Review
- Origins of Programmable Nucleases for Genome Engineering.Journal of molecular biology · 2016Review
- 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
- Epigenetic mechanisms underlying the pathogenesis of neurogenetic diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2014Review
- Controlling gene networks and cell fate with precision-targeted DNA-binding proteins and small-molecule-based genome readers.The Biochemical journal · 2014Review
- Article
- Writing and rewriting the epigenetic code of cancer cells: from engineered proteins to small molecules.Molecular pharmacology · 2013Review
- Compact designer TALENs for efficient genome engineering.Nature communications · 2013Article
- Complementation between inactive fragments of SssI DNA methyltransferase.BMC molecular biology · 2012Article
- Selective DNA demethylation by fusion of TDG with a sequence-specific DNA-binding domain.Epigenetics · 2012Article
- A novel zinc-finger nuclease platform with a sequence-specific cleavage module.Nucleic acids research · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The ability to target methylation to specific genomic sites would further the study of DNA methylation's biological role and potentially offer a tool for silencing gene expression and for treating diseases involving abnormal hypomethylation. The end-to-end fusion of DNA methyltransferases to zinc fingers has been shown to bias methylation to desired regions. However, the strategy is inherently limited because the methyltransferase domain remains active regardless of whether the zinc finger domain is bound at its cognate site and can methylate non-target sites. We demonstrate an alternative strategy in which fragments of a DNA methyltransferase, compromised in their ability to methylate DNA, are fused to two zinc fingers designed to bind 9 bp sites flanking a methylation target site. Using the naturally heterodimeric DNA methyltransferase M.EcoHK31I, which methylates the inner cytosine of 5'-YGGCCR-3', we demonstrate that this strategy can yield a methyltransferase capable of significant levels of methylation at the target site with undetectable levels of methylation at non-target sites in Escherichia coli. However, some non-target methylation could be detected at higher expression levels of the zinc finger methyltransferase indicating that further improvements will be necessary to attain the desired exclusive target specificity.
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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.