ArticleThe EMBO journal2016
TET-catalyzed oxidation of intragenic 5-methylcytosine regulates CTCF-dependent alternative splicing.
Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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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.
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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.
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Who cites it
75 citing papers in PubMed, 107 citations in OpenAlex.
- CTCF regulates wild-type and recombinant AAV gene expression by shaping viral chromatin.bioRxiv : the preprint server for biology · 2026Article
- A distinct subclade of AlkB family demethylases in ciliates safeguards the positional fidelity of eukaryotic NProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Context-specific regulatory genetic variation in MTOR dampens neutrophil-T cell crosstalk in pneumonia-associated sepsis.Nature communications · 2026Article
- From molecular damage to regulatory constraint: epigenetic and metabolic limits of cellular plasticity in aging.Frontiers in aging · 2026Review
- Epigenotoxicity: Decoding the epigenetic imprints of genotoxic agents and their implications for regulatory genetic toxicology.Environmental and molecular mutagenesis · 2025Review
- TEAMwork: Interplay of Post-Transcriptional Mechanisms, Epigenetics and Metabolism in (Auto-)Immunity.European journal of immunology · 2025Review
- Predicting differentially methylated cytosines in TET and DNMT3 knockout mutants via a large language model.Briefings in bioinformatics · 2025Article
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- Article
- A Compendium of G-Flipon Biological Functions That Have Experimental Validation.International journal of molecular sciences · 2024Review
- Predicting Differentially Methylated Cytosines in TET and DNMT3 Knockout Mutants via a Large Language Model.bioRxiv : the preprint server for biology · 2024Article
- Epigenetic control of skeletal muscle atrophy.Cellular & molecular biology letters · 2024Review
- Single-molecule imaging reveals a direct role of CTCF's zinc fingers in SA interaction and cluster-dependent RNA recruitment.Nucleic acids research · 2024Article
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- One-pot trimodal mapping of unmethylated, hydroxymethylated, and open chromatin sites unveils distinctive 5hmC roles at dynamic chromatin loci.Cell chemical biology · 2024Article
- TET (Ten-eleven translocation) family proteins: structure, biological functions and applications.Signal transduction and targeted therapy · 2023Review
- DNA strand asymmetry generated by CpG hemimethylation has opposing effects on CTCF binding.Nucleic acids research · 2023Article
- Hypoxia-induced loss of SRSF2-dependent DNA methylation promotes CTCF-mediated alternative splicing of VEGFA in breast cancer.iScience · 2023Article
- Review
- Synthetic lethal targeting of TET2-mutant haematopoietic stem and progenitor cells by XPO1 inhibitors.British journal of haematology · 2023Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Intragenic 5-methylcytosine and CTCF mediate opposing effects on pre-mRNA splicing: CTCF promotes inclusion of weak upstream exons through RNA polymerase II pausing, whereas 5-methylcytosine evicts CTCF, leading to exon exclusion. However, the mechanisms governing dynamic DNA methylation at CTCF-binding sites were unclear. Here, we reveal the methylcytosine dioxygenases TET1 and TET2 as active regulators of CTCF-mediated alternative splicing through conversion of 5-methylcytosine to its oxidation derivatives. 5-hydroxymethylcytosine and 5-carboxylcytosine are enriched at an intragenic CTCF-binding sites in the CD45 model gene and are associated with alternative exon inclusion. Reduced TET levels culminate in increased 5-methylcytosine, resulting in CTCF eviction and exon exclusion. In vitro analyses establish the oxidation derivatives are not sufficient to stimulate splicing, but efficiently promote CTCF association. We further show genomewide that reciprocal exchange of 5-hydroxymethylcytosine and 5-methylcytosine at downstream CTCF-binding sites is a general feature of alternative splicing in naïve and activated CD4(+) T cells. These findings significantly expand our current concept of the pre-mRNA "splicing code" to include dynamic intragenic DNA methylation catalyzed by the TET proteins.
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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.