ArticleScientific reports2015
The hypomethylating agent Decitabine causes a paradoxical increase in 5-hydroxymethylcytosine in human leukemia cells.
Article in Scientific reports, 2015. 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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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
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- Neocentromeres fail to maintain DNA methylation boundaries, driving CENP-A drift, instability, and chromosome missegregation.Cell reports · 2026Article
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- Advances in epigenetic treatment of adult T-cell leukemia/lymphoma: a comprehensive review.Clinical epigenetics · 2025Review
- Cytosine methylase and hydroxymethylase activity in mammalian mitochondria.Frontiers in cell and developmental biology · 2025Article
- The Advances in the Development of Epigenetic Modifications Therapeutic Drugs Delivery Systems.International journal of nanomedicine · 2024Review
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- Psychostimulant-induced aberrant DNA methylation in an in vitro model of human peripheral blood mononuclear cells.Clinical epigenetics · 2022Article
- Epigenetic Regulation in Uterine Fibroids-The Role of Ten-Eleven Translocation Enzymes and Their Potential Therapeutic Application.International journal of molecular sciences · 2022Review
- Decitabine-induced DNA methylation-mediated transcriptomic reprogramming in human breast cancer cell lines; the impact of DCK overexpression.Frontiers in pharmacology · 2022Article
- Targeting Germ Cell Tumors with the Newly Synthesized Flavanone-Derived Compound MLo1302 Efficiently Reduces Tumor Cell Viability and Induces Apoptosis and Cell Cycle Arrest.Pharmaceutics · 2021Article
- Multi and transgenerational epigenetic effects of di-(2-ethylhexyl) phthalate (DEHP) in liver.Toxicology and applied pharmacology · 2020Article
- Sodium valproate and 5-aza-2'-deoxycytidine differentially modulate DNA demethylation in G1 phase-arrested and proliferative HeLa cells.Scientific reports · 2019Article
- DNMT Inhibitors Increase Methylation in the Cancer Genome.Frontiers in pharmacology · 2019Article
- Vitamin C promotes decitabine or azacytidine induced DNA hydroxymethylation and subsequent reactivation of the epigenetically silenced tumour suppressorOncotarget · 2018Article
- Inhibition of DNA methyltransferase leads to increased genomic 5-hydroxymethylcytosine levels in hematopoietic cells.FEBS open bio · 2018Article
- MN1 overexpression is driven by loss of DNMT3B methylation activity in inv(16) pediatric AML.Oncogene · 2018Article
- Oxygen nanobubbles revert hypoxia by methylation programming.Scientific reports · 2017Article
- Determinants of orofacial clefting II: Effects of 5-Aza-2'-deoxycytidine on gene methylation during development of the first branchial arch.Reproductive toxicology (Elmsford, N.Y.) · 2017Article
- Technical advances in global DNA methylation analysis in human cancers.Journal of biological engineering · 2017Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The USFDA approved "epigenetic drug", Decitabine, exerts its effect by hypomethylating DNA, demonstrating the pivotal role aberrant genome-wide DNA methylation patterns play in cancer ontology. Using sensitive technologies in a cellular model of Acute Myeloid Leukemia, we demonstrate that while Decitabine reduces the global levels of 5-methylcytosine (5mC), it results in paradoxical increase of 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) levels. Hitherto, the only biological mechanism known to generate 5hmC, 5fC and 5caC, involving oxidation of 5mC by members of Ten-Eleven-Translocation (TET) dioxygenase family, was not observed to undergo any alteration during DAC treatment. Using a multi-compartmental model of DNA methylation, we show that partial selectivity of TET enzymes for hemi-methylated CpG dinucleotides could lead to such alterations in 5hmC content. Furthermore, we investigated the binding of TET1-catalytic domain (CD)-GFP to DNA by Fluorescent Correlation Spectroscopy in live cells and detected the gradual increase of the DNA bound fraction of TET1-CD-GFP after treatment with Decitabine. Our study provides novel insights on the therapeutic activity of DAC in the backdrop of the newly discovered derivatives of 5mC and suggests that 5hmC has the potential to serve as a biomarker for monitoring the clinical success of patients receiving DAC.
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