Cited by 1,021Epigenetics and DNA MethylationGenomics and Chromatin DynamicsGenetic Syndromes and Imprinting

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TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity

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Williams, Kristine, Christensen, Jesper, Pedersen, Marianne Terndrup, Johansen, Jens V., Cloos, Paul A. C., Rappsilber, Juri, Helin, Kristian·2011·Nature

DOI 10.1038/nature10066PMC PMC3408592

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Abstract

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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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: Williams, Kristine
Christensen, Jesper
Pedersen, Marianne Terndrup
Johansen, Jens V.
Cloos, Paul A. C.
Rappsilber, Juri
Helin, Kristian
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2011-04-13
Volume: 473
Issue: 7347
Pages: 343-348
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature10066
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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