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TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity

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  • Kristine Williams

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5
    Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5)

  • Jesper Christensen

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5
    Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5)

  • Marianne Terndrup Pedersen

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5
    Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5)

  • Jens V. Johansen

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5
    The Bioinformatics Centre, University of Copenhagen, Ole Maaløes Vej 5)

  • Paul A. C. Cloos

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5
    Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5)

  • Juri Rappsilber

    (Wellcome Trust Centre for Cell Biology, University of Edinburgh)

  • Kristian Helin

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5
    Centre for Epigenetics, University of Copenhagen, Ole Maaløes Vej 5)

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.

Suggested Citation

  • Kristine Williams & Jesper Christensen & Marianne Terndrup Pedersen & Jens V. Johansen & Paul A. C. Cloos & Juri Rappsilber & Kristian Helin, 2011. "TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity," Nature, Nature, vol. 473(7347), pages 343-348, May.
    • Handle: RePEc:nat:nature:v:473:y:2011:i:7347:d:10.1038_nature10066
    DOI: 10.1038/nature10066
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    Cited by:

    1. Youping Tian & Xiaoyu Zhou & Maohua Miao & De-kun Li & Ziliang Wang & Runsheng Li & Hong Liang & Wei Yuan, 2018. "Association of Bisphenol A Exposure with LINE-1 Hydroxymethylation in Human Semen," IJERPH, MDPI, vol. 15(8), pages 1-10, August.
    2. Lijun Wang & Xiuling You & Dengfeng Ruan & Rui Shao & Hai-Qiang Dai & Weiliang Shen & Guo-Liang Xu & Wanlu Liu & Weiguo Zou, 2022. "TET enzymes regulate skeletal development through increasing chromatin accessibility of RUNX2 target genes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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