ArticleGenome biology2016
In vivo genome-wide profiling reveals a tissue-specific role for 5-formylcytosine.
Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 68 citations in OpenAlex.
- Genomic sequence context differentially impacts stepwise oxidation by TET enzymes to shape DNA hydroxymethylation landscapes.Nucleic acids research · 2026Article
- Positive TAZ-TDG feedback loop drives proneural-to-mesenchymal transition to promote glioblastoma progression.Journal of translational medicine · 2026Article
- 5-Formylcytosine functions as a chemical regulator of nucleosome positioning.Nature communications · 2026Article
- Cell identity and 5-hydroxymethylcytosine.Epigenetics & chromatin · 2025Review
- Sperm chromatin accessibility's involvement in the intergenerational effects of stress hormone receptor activation.Translational psychiatry · 2023Article
- Protonation-Dependent Sequencing of 5-Formylcytidine in RNA.Biochemistry · 2022Article
- Direct and Base Excision Repair-Mediated Regulation of a GC-RichInternational journal of molecular sciences · 2021Article
- LINE-1 transcription in round spermatids is associated with accretion of 5-carboxylcytosine in their open reading frames.Communications biology · 2021Article
- Genomic Uracil and Aberrant Profile of Demethylation Intermediates in Epigenetics and Hematologic Malignancies.International journal of molecular sciences · 2021Review
- Active DNA demethylation-The epigenetic gatekeeper of development, immunity, and cancer.Advanced genetics (Hoboken, N.J.) · 2021Review
- TET2 is a component of the estrogen receptor complex and controls 5mC to 5hmC conversion at estrogen receptor cis-regulatory regions.Cell reports · 2021Article
- Active turnover of DNA methylation during cell fate decisions.Nature reviews. Genetics · 2021Review
- Reduced Bisulfite Sequencing: Quantitative Base-Resolution Sequencing of 5-Formylcytosine.Methods in molecular biology (Clifton, N.J.) · 2021Article
- 5-Formylcytosine landscapes of human preimplantation embryos at single-cell resolution.PLoS biology · 2020Article
- 5-formylcytosine and 5-hydroxymethyluracil as surrogate markers of TET2 and SF3B1 mutations in myelodysplastic syndrome, respectively.Haematologica · 2020Article
- Mass spectrometry reveals the presence of specific set of epigenetic DNA modifications in the Norway spruce genome.Scientific reports · 2019Article
- DNAmod: the DNA modification database.Journal of cheminformatics · 2019Article
- 5-Formylcytosine organizes nucleosomes and forms Schiff base interactions with histones in mouse embryonic stem cells.Nature chemistry · 2018Article
- Dysregulation and prognostic potential of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) levels in prostate cancer.Clinical epigenetics · 2018Article
- The TET enzymes.Cellular and molecular life sciences : CMLS · 2018Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundGenome-wide methylation of cytosine can be modulated in the presence of TET and thymine DNA glycosylase (TDG) enzymes. TET is able to oxidise 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TDG can excise the oxidative products 5fC and 5caC, initiating base excision repair. These modified bases are stable and detectable in the genome, suggesting that they could have epigenetic functions in their own right. However, functional investigation of the genome-wide distribution of 5fC has been restricted to cell culture-based systems, while its in vivo profile remains unknown.
resultsHere, we describe the first analysis of the in vivo genome-wide profile of 5fC across a range of tissues from both wild-type and Tdg-deficient E11.5 mouse embryos. Changes in the formylation profile of cytosine upon depletion of TDG suggest TET/TDG-mediated active demethylation occurs preferentially at intron-exon boundaries and reveals a major role for TDG in shaping 5fC distribution at CpG islands. Moreover, we find that active enhancer regions specifically exhibit high levels of 5fC, resulting in characteristic tissue-diagnostic patterns, which suggest a role in embryonic development.
conclusionsThe tissue-specific distribution of 5fC can be regulated by the collective contribution of TET-mediated oxidation and excision by TDG. The in vivo profile of 5fC during embryonic development resembles that of embryonic stem cells, sharing key features including enrichment of 5fC in enhancer and intragenic regions. Additionally, by investigating mouse embryo 5fC profiles in a tissue-specific manner, we identify targeted enrichment at active enhancers involved in tissue development.
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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.