title: TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity.
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.
authors.affiliation: Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark.
authors.forename: Kristine
authors.initials: K
authors.lastname: Williams
authors.forename: Jesper
authors.initials: J
authors.lastname: Christensen
authors.forename: Marianne Terndrup
authors.initials: MT
authors.lastname: Pedersen
authors.forename: Jens V
authors.initials: JV
authors.lastname: Johansen
authors.forename: Paul A C
authors.initials: PA
authors.lastname: Cloos
authors.forename: Juri
authors.initials: J
authors.lastname: Rappsilber
authors.forename: Kristian
authors.initials: K
authors.lastname: Helin
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D002460:Cell Line; D018899:CpG Islands / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D051379:Mice; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C099683:SIN3A transcription factor; C540839:TET1 protein, mouse; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D056264:Sin3 Histone Deacetylase and Corepressor Complex