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

doi:10.1038/nature10066

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

723 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Nature
Vol/bind	473
Udgave nummer	7347
Sider (fra-til)	343-8
Antal sider	6
ISSN	0028-0836
DOI	https://doi.org/10.1038/nature10066
Status	Udgivet - 19 maj 2011

Adgang til dokumentet

10.1038/nature10066

Citationsformater

@article{5b6a03e4f127401382f7456bfa548826,

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.",

author = "Kristine Williams and Jesper Christensen and Pedersen, {Marianne Terndrup} and Johansen, {Jens V} and Cloos, {Paul A C} and Juri Rappsilber and Kristian Helin",

year = "2011",

month = may,

day = "19",

doi = "10.1038/nature10066",

language = "English",

volume = "473",

pages = "343--8",

journal = "Nature",

issn = "0028-0836",

publisher = "nature publishing group",

number = "7347",

}

TY - JOUR

T1 - TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity

AU - Williams, Kristine

AU - Christensen, Jesper

AU - Pedersen, Marianne Terndrup

AU - Johansen, Jens V

AU - Cloos, Paul A C

AU - Rappsilber, Juri

AU - Helin, Kristian

PY - 2011/5/19

Y1 - 2011/5/19

N2 - 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.

AB - 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.

U2 - 10.1038/nature10066

DO - 10.1038/nature10066

M3 - Journal article

C2 - 21490601

SN - 0028-0836

VL - 473

SP - 343

EP - 348

JO - Nature

JF - Nature

IS - 7347

ER -

TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater