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TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity

Kristine Williams, Jesper Christensen, Marianne Terndrup Pedersen, Jens V. Johansen, Paul A. C. Cloos, Juri Rappsilber and Kristian Helin ()
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Kristine Williams: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5
Jesper Christensen: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5
Marianne Terndrup Pedersen: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5
Jens V. Johansen: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5
Paul A. C. Cloos: Biotech Research and Innovation Centre (BRIC), 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

Nature, 2011, vol. 473, issue 7347, 343-348

Abstract: 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.

Date: 2011
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DOI: 10.1038/nature10066

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