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TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity.

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.

Pubmed ID: 21490601

Authors

  • Williams K
  • Christensen J
  • Pedersen MT
  • Johansen JV
  • Cloos PA
  • Rappsilber J
  • Helin K

Journal

Nature

Publication Data

May 19, 2011

Associated Grants

  • Agency: Wellcome Trust, Id: 084229

Mesh Terms

  • Animals
  • Cell Line
  • CpG Islands
  • Cytosine
  • DNA (Cytosine-5-)-Methyltransferase
  • DNA Methylation
  • DNA-Binding Proteins
  • Down-Regulation
  • Embryonic Stem Cells
  • Gene Knockdown Techniques
  • Mice
  • Protein Binding
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Transcription Initiation Site
  • Transcription, Genetic