ArticleEpigenetics2017
Targeted DNA demethylation in human cells by fusion of a plant 5-methylcytosine DNA glycosylase to a sequence-specific DNA binding domain.
Article in Epigenetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- DNA Methylation as a Programmable Information Layer: From Molecular Marks to Disease State Engineering.International journal of molecular sciences · 2026Review
- Versatile molecular tools enabling customizable DNA methylation editing in Arabidopsis.Nature communications · 2025Article
- Vector-free intra-airway in vivo epigenetic editing.Trends in biotechnology · 2025Article
- Precision epigenetic editing: Technological advances, enduring challenges, and therapeutic applications.Cell chemical biology · 2024Review
- Base Excision DNA Repair in Plants:International journal of molecular sciences · 2023Review
- Targeted DNA Demethylation: Vectors, Effectors and Perspectives.Biomedicines · 2023Review
- Molecular basis of the plant ROS1-mediated active DNA demethylation.Nature plants · 2023Article
- Sry-related High Mobility Group Box 17 Functions as a Tumor Suppressor by Antagonizing the Wingless-related Integration Site Pathway.Journal of cancer prevention · 2020Review
- Site-Specific DNA Demethylation as a Potential Target for Cancer Epigenetic Therapy.Epigenetics insights · 2020Review
- Review
- Active DNA Demethylation in Plants.International journal of molecular sciences · 2019Review
- DNA methylation and de-methylation using hybrid site-targeting proteins.Genome biology · 2018Review
- Epigenetic signatures in cardiac fibrosis, special emphasis on DNA methylation and histone modification.Heart failure reviews · 2018Review
- Harnessing natural DNA modifying activities for editing of the genome and epigenome.Current opinion in chemical biology · 2018Review
- Epigenetic Regulation of Myofibroblast Phenotypes in Fibrosis.Current pathobiology reports · 2018Article
- DNA methylation reprogramming of human cancer cells by expression of a plant 5-methylcytosine DNA glycosylase.Epigenetics · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation is a crucial epigenetic mark associated to gene silencing, and its targeted removal is a major goal of epigenetic editing. In animal cells, DNA demethylation involves iterative 5mC oxidation by TET enzymes followed by replication-dependent dilution and/or replication-independent DNA repair of its oxidized derivatives. In contrast, plants use specific DNA glycosylases that directly excise 5mC and initiate its substitution for unmethylated C in a base excision repair process. In this work, we have fused the catalytic domain of Arabidopsis ROS1 5mC DNA glycosylase (ROS1_CD) to the DNA binding domain of yeast GAL4 (GBD). We show that the resultant GBD-ROS1_CD fusion protein binds specifically a GBD-targeted DNA sequence in vitro. We also found that transient in vivo expression of GBD-ROS1_CD in human cells specifically reactivates transcription of a methylation-silenced reporter gene, and that such reactivation requires both ROS1_CD catalytic activity and GBD binding capacity. Finally, we show that reactivation induced by GBD-ROS1_CD is accompanied by decreased methylation levels at several CpG sites of the targeted promoter. All together, these results show that plant 5mC DNA glycosylases can be used for targeted active DNA demethylation in human cells.
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