ArticleBioconjugate chemistry2010
Targeted DNA methylation by a DNA methyltransferase coupled to a triple helix forming oligonucleotide to down-regulate the epithelial cell adhesion molecule.
Article in Bioconjugate chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Targeted DNA triplex-forming oligonucleotide liposome for pulmonary fibrosis gene therapy.Cell reports. Medicine · 2026Article
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Genome wide inherited modifications of the tomato epigenome by trans-activated bacterial CG methyltransferase.Cellular and molecular life sciences : CMLS · 2024Article
- Conversion of the CG specific M.MpeI DNA methyltransferase into an enzyme predominantly methylating CCA and CCC sites.Nucleic acids research · 2024Article
- Lowering DNA binding affinity of SssI DNA methyltransferase does not enhance the specificity of targeted DNA methylation in E. coli.Scientific reports · 2021Article
- KRAB-Induced Heterochromatin Effectively SilencesInternational journal of molecular sciences · 2020Article
- The importance of DNA methylation of exons on alternative splicing.RNA (New York, N.Y.) · 2018Article
- The past and presence of gene targeting: from chemicals and DNA via proteins to RNA.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- Epigenome engineering in cancer: fairytale or a realistic path to the clinic?Frontiers in oncology · 2015Review
- Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter.Nucleic acids research · 2014Article
- Article
- Targeted methylation of the epithelial cell adhesion molecule (EpCAM) promoter to silence its expression in ovarian cancer cells.PloS one · 2014Article
- Writing and rewriting the epigenetic code of cancer cells: from engineered proteins to small molecules.Molecular pharmacology · 2013Review
- Article
- Epigenetic Editing: targeted rewriting of epigenetic marks to modulate expression of selected target genes.Nucleic acids research · 2012Review
- Complementation between inactive fragments of SssI DNA methyltransferase.BMC molecular biology · 2012Article
- Article
- Targeted DNA methylation using an artificially bisected M.HhaI fused to zinc fingers.PloS one · 2012Article
- Transcription factors and molecular epigenetic marks underlying EpCAM overexpression in ovarian cancer.British journal of cancer · 2011Article
- Small-molecule regulators that mimic transcription factors.Biochimica et biophysica actaReview
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epithelial cell adhesion molecule (EpCAM) is a membrane glycoprotein that has been identified as a marker of cancer-initiating cells. EpCAM is highly expressed on most carcinomas, and transient silencing of EpCAM expression leads to reduced oncogenic potential. To silence the EpCAM gene in a persistent manner via targeted DNA methylation, a low activity mutant (C141S) of the CpG-specific DNA methyltransferase M.SssI was coupled to a triple-helix-forming oligonucleotide (TFO-C141S) specifically designed for the EpCAM gene. Reporter plasmids encoding the green fluorescent protein under control of different EpCAM promoter fragments were treated with the TFO-C141S conjugate to determine the specificity of targeted DNA methylation in the context of a functional EpCAM promoter. Treatment of the plasmids with TFO-C141S resulted in efficient and specific methylation of the targeted CpG located directly downstream of the triple helix forming site (TFS). No background DNA methylation was observed neither in a 700 bp region of the EpCAM promoter nor in a 400 bp region of the reporter gene downstream of the TFS. Methylation of the target CpG did not have a detectable effect on promoter activity. This study shows that the combination of a specific TFO and a reduced activity methyltransferase variant can be used to target DNA methylation to predetermined sites with high specificity, allowing determination of crucial CpGs for promoter activity.
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