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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
5-Methylcytosine / analogs & derivatives
-
Animals
-
Cell Line
-
CpG Islands / genetics
-
Cytosine / analogs & derivatives*
-
Cytosine / metabolism
-
DNA (Cytosine-5-)-Methyltransferase 1
-
DNA (Cytosine-5-)-Methyltransferases / genetics
-
DNA Methylation*
-
DNA-Binding Proteins / deficiency
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Down-Regulation
-
Embryonic Stem Cells / cytology
-
Embryonic Stem Cells / metabolism
-
Gene Knockdown Techniques
-
Mice
-
Protein Binding
-
Proto-Oncogene Proteins / deficiency
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / metabolism*
-
Repressor Proteins / metabolism
-
Sin3 Histone Deacetylase and Corepressor Complex
-
Transcription Initiation Site
-
Transcription, Genetic*
Substances
-
DNA-Binding Proteins
-
Proto-Oncogene Proteins
-
Repressor Proteins
-
SIN3A transcription factor
-
TET1 protein, mouse
-
5-hydroxymethylcytosine
-
5-Methylcytosine
-
Cytosine
-
DNA (Cytosine-5-)-Methyltransferase 1
-
DNA (Cytosine-5-)-Methyltransferases
-
Sin3 Histone Deacetylase and Corepressor Complex