ArticleProceedings of the National Academy of Sciences of the United States of America2010
Identification of RING finger protein 4 (RNF4) as a modulator of DNA demethylation through a functional genomics screen.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 71 citations in OpenAlex.
- SUMOylation enhances DNMT1 function to repress mega-intergenic RNAs and viral mimicry.Nature genetics · 2026Article
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- Protein-Protein Interactions in Base Excision Repair.Biomolecules · 2025Review
- Article
- Decitabine cytotoxicity is promoted by dCMP deaminase DCTD and mitigated by SUMO-dependent E3 ligase TOPORS.The EMBO journal · 2024Article
- SUMO and the DNA damage response.Biochemical Society transactions · 2024Review
- RNF4 sustains Myc-driven tumorigenesis by facilitating DNA replication.The Journal of clinical investigation · 2024Article
- Review
- Gadd45 in DNA Demethylation and DNA Repair.Advances in experimental medicine and biology · 2022Article
- Review
- RNF4 Regulates the BLM Helicase in Recovery From Replication Fork Collapse.Frontiers in genetics · 2021Article
- Article
- CB1R-Mediated Activation of Caspase-3 Causes Epigenetic and Neurobehavioral Abnormalities in Postnatal Ethanol-Exposed Mice.Frontiers in molecular neuroscience · 2018Article
- The Biology of SUMO-Targeted Ubiquitin Ligases in Drosophila Development, Immunity, and Cancer.Journal of developmental biology · 2018Review
- A Lysine Desert Protects a Novel Domain in the Slx5-Slx8 SUMO Targeted Ub Ligase To Maintain Sumoylation Levels inGenetics · 2017Article
- RNF4-Dependent Oncogene Activation by Protein Stabilization.Cell reports · 2016Article
- DNA methylation in Huntington's disease: Implications for transgenerational effects.Neuroscience letters · 2016Review
- Analysis of Small Ubiquitin-Like Modifier (SUMO) Targets Reflects the Essential Nature of Protein SUMOylation and Provides Insight to Elucidate the Role of SUMO in Plant Development.Plant physiology · 2015Article
- Ubiquitin-specific Protease 11 (USP11) Deubiquitinates Hybrid Small Ubiquitin-like Modifier (SUMO)-Ubiquitin Chains to Counteract RING Finger Protein 4 (RNF4).The Journal of biological chemistry · 2015Article
- HDAC inhibition imparts beneficial transgenerational effects in Huntington's disease mice via altered DNA and histone methylation.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation is an important epigenetic modification involved in transcriptional regulation, nuclear organization, development, aging, and disease. Although DNA methyltransferases have been characterized, the mechanisms for DNA demethylation remain poorly understood. Using a cell-based reporter assay, we performed a functional genomics screen to identify genes involved in DNA demethylation. Here we show that RNF4 (RING finger protein 4), a SUMO-dependent ubiquitin E3-ligase previously implicated in maintaining genome stability, plays a key role in active DNA demethylation. RNF4 reactivates methylation-silenced reporters and promotes global DNA demethylation. Rnf4 deficiency is embryonic lethal with higher levels of methylation in genomic DNA. Mechanistic studies show that RNF4 interacts with and requires the base excision repair enzymes TDG and APE1 for active demethylation. This activity appears to occur by enhancing the enzymatic activities that repair DNA G:T mismatches generated from methylcytosine deamination. Collectively, our study reveals a unique function for RNF4, which may serve as a direct link between epigenetic DNA demethylation and DNA repair in mammalian cells.
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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.