ArticleCell cycle (Georgetown, Tex.)2014
RFTS-deleted DNMT1 enhances tumorigenicity with focal hypermethylation and global hypomethylation.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 20 citations in OpenAlex.
- Functional and Epigenomic Consequences ofInternational journal of molecular sciences · 2026Article
- The Double-Edged Sword of Genomic DNA Methylation: Orchestrating Gastric Carcinogenesis and Shaping Precision Oncology.Oncology research · 2026Review
- System genetic analysis of intestinal cancer and periodontitis development as influenced by aging and diabesity using Collaborative Cross mice.Animal models and experimental medicine · 2025Review
- Downregulation of DUOX1 function contributes to aging-related impairment of innate airway injury responses and accelerated senile emphysema.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Review
- Circulating MIR148A associates with sensitivity to adiponectin levels in human metabolic surgery for weight lossEndocrine connections · 2018Article
- Article
- Paradoxical roles of dual oxidases in cancer biology.Free radical biology & medicine · 2017Review
- A Tox21 Approach to Altered Epigenetic Landscapes: Assessing Epigenetic Toxicity Pathways Leading to Altered Gene Expression and Oncogenic Transformation In Vitro.International journal of molecular sciences · 2017Review
- DUOX1 silencing in lung cancer promotes EMT, cancer stem cell characteristics and invasive properties.Oncogenesis · 2016Article
- Article
- DNA methyltransferase 1 mutations and mitochondrial pathology: is mtDNA methylated?Frontiers in genetics · 2015Article
- Article
- DNMT1-associated DNA methylation changes in cancer.Cell cycle (Georgetown, Tex.) · 2015Article
- Suppression of TET1-dependent DNA demethylation is essential for KRAS-mediated transformation.Cell reports · 2014Article
Corrections and comments
- Commented on by
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Site-specific hypermethylation of tumor suppressor genes accompanied by genome-wide hypomethylation are epigenetic hallmarks of malignancy. However, the molecular mechanisms that drive these linked changes in DNA methylation remain obscure. DNA methyltransferase 1 (DNMT1), the principle enzyme responsible for maintaining methylation patterns is commonly dysregulated in tumors. Replication foci targeting sequence (RFTS) is an N-terminal domain of DNMT1 that inhibits DNA-binding and catalytic activity, suggesting that RFTS deletion would result in a gain of DNMT1 function. However, a substantial body of data suggested that RFTS is required for DNMT1 activity. Here, we demonstrate that deletion of RFTS alters DNMT1-dependent DNA methylation during malignant transformation. Compared to full-length DNMT1, ectopic expression of hyperactive DNMT1-ΔRFTS caused greater malignant transformation and enhanced promoter methylation with condensed chromatin structure that silenced DAPK and DUOX1 expression. Simultaneously, deletion of RFTS impaired DNMT1 chromatin association with pericentromeric Satellite 2 (SAT2) repeat sequences and produced DNA demethylation at SAT2 repeats and globally. To our knowledge, RFTS-deleted DNMT1 is the first single factor that can reprogram focal hypermethylation and global hypomethylation in parallel during malignant transformation. Our evidence suggests that the RFTS domain of DNMT1 is a target responsible for epigenetic changes in cancer.
Indexed as
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.