Hydroxylation of 5-methylcytosine by Tet2 maintains the active state of the mammalian Hoxa cluster

Michael T. Bocker, Francesca Tuorto, Günter Raddatz, Tanja Musch, Feng Chun Yang, Mingjiang Xu, Frank Lyko, Achim Breiling

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Differentiation is accompanied by extensive epigenomic reprogramming, leading to the repression of stemness factors and the transcriptional maintenance of activated lineage-specific genes. Here we use the mammalian Hoxa cluster of developmental genes as a model system to follow changes in DNA modification patterns during retinoic acid-induced differentiation. We find the inactive cluster to be marked by defined patterns of 5-methylcytosine (5mC). Upon the induction of differentiation, the active anterior part of the cluster becomes increasingly enriched in 5-hydroxymethylcytosine (5hmC), following closely the colinear activation pattern of the gene array, which is paralleled by the reduction of 5mC. Depletion of the 5hmC generating dioxygenase Tet2 impairs the maintenance of Hoxa activity and partially restores 5mC levels. Our results indicate that gene-specific 5mC-5hmC conversion by Tet2 is crucial for the maintenance of active chromatin states at lineage-specific loci.

Original languageEnglish
Article number818
JournalNature Communications
Volume3
DOIs
StatePublished - 2012

Fingerprint

5-Methylcytosine
Hydroxylation
genes
Genes
maintenance
Maintenance
Developmental Genes
Dioxygenases
chromatin
loci
Tretinoin
Epigenomics
Transcriptional Activation
Chromatin
induction
depletion
deoxyribonucleic acid
Chemical activation
activation
acids

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Bocker, M. T., Tuorto, F., Raddatz, G., Musch, T., Yang, F. C., Xu, M., ... Breiling, A. (2012). Hydroxylation of 5-methylcytosine by Tet2 maintains the active state of the mammalian Hoxa cluster. Nature Communications, 3, [818]. https://doi.org/10.1038/ncomms1826

Hydroxylation of 5-methylcytosine by Tet2 maintains the active state of the mammalian Hoxa cluster. / Bocker, Michael T.; Tuorto, Francesca; Raddatz, Günter; Musch, Tanja; Yang, Feng Chun; Xu, Mingjiang; Lyko, Frank; Breiling, Achim.

In: Nature Communications, Vol. 3, 818, 2012.

Research output: Contribution to journalArticle

Bocker, MT, Tuorto, F, Raddatz, G, Musch, T, Yang, FC, Xu, M, Lyko, F & Breiling, A 2012, 'Hydroxylation of 5-methylcytosine by Tet2 maintains the active state of the mammalian Hoxa cluster', Nature Communications, vol. 3, 818. https://doi.org/10.1038/ncomms1826
Bocker, Michael T. ; Tuorto, Francesca ; Raddatz, Günter ; Musch, Tanja ; Yang, Feng Chun ; Xu, Mingjiang ; Lyko, Frank ; Breiling, Achim. / Hydroxylation of 5-methylcytosine by Tet2 maintains the active state of the mammalian Hoxa cluster. In: Nature Communications. 2012 ; Vol. 3.
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