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, Kristian Helin

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)343-U472
Number of pages7
JournalNature
Volume473
Issue number7347
DOIs
Publication statusPublished - 19 May 2011

Keywords / Materials (for Non-textual outputs)

  • EMBRYONIC STEM-CELLS
  • SELF-RENEWAL
  • 5-HYDROXYMETHYLCYTOSINE
  • LINEAGE
  • WIDE
  • DIFFERENTIATION
  • SPECIFICATION
  • PLURIPOTENT
  • CONVERSION
  • PROMOTERS

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