ArticlePloS one2015
Tissue-Specific Differences in DNA Modifications (5-Hydroxymethylcytosine, 5-Formylcytosine, 5-Carboxylcytosine and 5-Hydroxymethyluracil) and Their Interrelationships.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- Relationship between Prostate Cancer and Benign Hyperplasia: Role of Inflammation-Induced Oxidative Stress, Vitamin C, and Epigenetics.The world journal of men's health · 2026Review
- Mechanisms of hepatic dysfunction in Nile tilapia (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Active DNA demethylation upstream of rod-photoreceptor fate determination is required for retinal development.PLoS biology · 2025Article
- Pioneering contribution of Professor Bruce Ames to early development in biochemical aspects of oxidatively generated damage to DNA.Frontiers in molecular biosciences · 2025Review
- Epigenetic DNA modifications and vitamin C in prostate cancer and benign prostatic hyperplasia: Exploring similarities, disparities, and pathogenic implications.Neoplasia (New York, N.Y.) · 2024Article
- Non-canonical bases differentially represented in the sex chromosomes of the dioecious plant Silene latifolia.Journal of experimental botany · 2024Article
- Ultrasensitive Simultaneous Detection of Multiple Rare Modified Nucleosides as Promising Biomarkers in Low-Put Breast Cancer DNA Samples for Clinical Multi-Dimensional Diagnosis.Molecules (Basel, Switzerland) · 2022Article
- Review
- A DNA adductome analysis revealed a reduction in the global level of C5-hydroxymethyl-2'-deoxycytidine in the non-tumoral upper urinary tract mucosa of urothelial carcinoma patients.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Article
- Translesion Synthesis Past 5-Formylcytosine-Mediated DNA-Peptide Cross-Links by hPolη Is Dependent on the Local DNA Sequence.Biochemistry · 2021Article
- Article
- Immunohistochemical evaluation of nuclear 5-hydroxymethylcytosine (5-hmC) accurately distinguishes malignant pleural mesothelioma from benign mesothelial proliferations.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2019Article
- Genomic landscape of oxidative DNA damage and repair reveals regioselective protection from mutagenesis.Genome biology · 2018Article
- 5-Formylcytosine mediated DNA-protein cross-links block DNA replication and induce mutations in human cells.Nucleic acids research · 2018Article
- In vivo evidence of ascorbate involvement in the generation of epigenetic DNA modifications in leukocytes from patients with colorectal carcinoma, benign adenoma and inflammatory bowel disease.Journal of translational medicine · 2018Article
- Oxidation Products of 5-Methylcytosine are Decreased in Senescent Cells and Tissues of Progeroid Mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2018Article
- High Performance Liquid Chromatography Separation of Epigenetic Cytosine Variants.Methods and protocols · 2018Article
- A Lexicon of DNA Modifications: Their Roles in Embryo Development and the Germline.Frontiers in cell and developmental biology · 2018Review
- Uracil Accumulation and Mutagenesis Dominated by Cytosine Deamination in CpG Dinucleotides in Mice Lacking UNG and SMUG1.Scientific reports · 2017Article
- APOBEC3A efficiently deaminates methylated, but not TET-oxidized, cytosine bases in DNA.Nucleic acids research · 2017Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundReplication-independent active/enzymatic demethylation may be an important process in the functioning of somatic cells. The most plausible mechanisms of active 5-methylcytosine demethylation, leading to activation of previously silenced genes, involve ten-eleven translocation (TET) proteins that participate in oxidation of 5-methylcytosine to 5-hydroxymethylcytosine which can be further oxidized to 5-formylcytosine and 5-carboxylcytosine. Recently, 5-hydroxymethylcytosine was demonstrated to be a relatively stable modification, and the previously observed substantial differences in the level of this modification in various murine tissues were shown to depend mostly on cell proliferation rate. Some experimental evidence supports the hypothesis that 5-hydroxymethyluracil may be also generated by TET enzymes and has epigenetic functions.
resultsUsing an isotope-dilution automated online two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry, we have analyzed, for the first time, all the products of active DNA demethylation pathway: 5-methyl-2'-deoxycytidine, 5-hydroxymethyl-2'-deoxycytidine, 5-formyl-2'-deoxycytidine and 5-carboxyl-2'-deoxycytidine, as well as 5-hydroxymethyl-2'-deoxyuridine, in DNA isolated from various rat and porcine tissues. A strong significant inverse linear correlation was found between the proliferation rate of cells and the global level of 5-hydroxymethyl-2'-deoxycytidine in both porcine (R2 = 0.88) and rat tissues (R2 = 0.83); no such relationship was observed for 5-formyl-2'-deoxycytidine and 5-carboxyl-2'-deoxycytidine. Moreover, a substrate-product correlation was demonstrated for the two consecutive steps of iterative oxidation pathway: between 5-hydroxymethyl-2'-deoxycytidine and its product 5-formyl-2'-deoxycytidine, as well as between 5-formyl-2'-deoxycytidine and 5-carboxyl-2'-deoxycytidine (R2 = 0.60 and R2 = 0.71, respectively).
conclusionsGood correlations within the substrate-product sets of iterative oxidation pathway may suggest that a part of 5-formyl-2'-deoxycytidine and/or 5-carboxyl-2'-deoxycytidine can be directly linked to a small portion of 5-hydroxymethyl-2'-deoxycytidine which defines the active demethylation process.
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