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TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity
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Enzymes catalysing the methylation of the 5-position of cytosine (mC) have essential roles in regulating gene expression and maintaining cellular identity. Recently, TET1 was found to hydroxylate the methyl group of mC, converting it to 5-hydroxymethyl cytosine (hmC). Here we show that TET1 binds throughout the genome of embryonic stem cells, with the majority of binding sites located at transcription start sites (TSSs) of CpG-rich promoters and within genes. The hmC modification is found in gene bodies and in contrast to mC is also enriched at CpG-rich TSSs. We provide evidence further that TET1 has a role in transcriptional repression. TET1 binds a significant proportion of Polycomb group target genes. Furthermore, TET1 associates and colocalizes with the SIN3A co-repressor complex. We propose that TET1 fine-tunes transcription, opposes aberrant DNA methylation at CpG-rich sequences and thereby contributes to the regulation of DNA methylation fidelity.
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“identifying 22 differentially expressed E3 ligase genes that may undergo epigenetic regulation by Tet1 (supplemental Table 1).”
From RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity by modulating ferroportin degradation (2021) · cites this paper as [47]
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“This is perhaps unsurprising since HDAC1/2 themselves (Fig. 4C) and their related complex components, Sin3A37 and LSD138, all map within the vicinity of TSS.”
From Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo (2018) · cites this paper as [37]
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Metadata
- Authors
- Williams, K., Christensen, J., Pedersen, M. T., Johansen, J. V., Cloos, P. A. C., Rappsilber, J., & Helin, K.
- Affiliations
- University of Copenhagen (DK)
- Wellcome Centre for Cell Biology (GB)
- Corresponding author
- Helin, Kristian
- ORCID
- Venue
- Nature
- Published
- 2011-04-13
- Volume
- 473
- Issue
- 7347
- Pages
- 343-348
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3408592
- OpenAlex
- W2014623973
- Cited by
- 1,021
- References
- 30
- Citations by year
- 2026: 23 · 2025: 29 · 2024: 29 · 2023: 37 · 2022: 44 · 2021: 57 · 2020: 49 · 2019: 55 · 2018: 63 · 2017: 65 · 2016: 87 · 2015: 72 · 2014: 108 · 2013: 125 · 2012: 114
- FWCI
- 53.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (084229)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- TET1, 5-hydroxymethylcytosine, DNA demethylation, transcription start sites, transcriptional repression, mouse embryonic stem cells, TET enzymes, genome-wide binding sites
- MeSH terms
- DNA (Cytosine-5-)-Methyltransferase 1, Animals, Cell Line, Cytosine, DNA (Cytosine-5-)-Methyltransferases, DNA-Binding Proteins, Protein Binding, Proto-Oncogene Proteins, Repressor Proteins, Transcription, Genetic, Down-Regulation, CpG Islands, DNA Methylation, Transcription Initiation Site, 5-Methylcytosine, Mice, Embryonic Stem Cells, Gene Knockdown Techniques, Sin3 Histone Deacetylase and Corepressor Complex
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