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.
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
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
Nature
Date: May. 19, 2011
PubMed ID: 21490601
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