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 journalArticlepeer-review

62 Scopus citations


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 (US)
Article number818
JournalNature communications
StatePublished - 2012
Externally publishedYes

ASJC Scopus subject areas

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


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