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Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster

Author

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  • Michael T. Bocker

    (DKFZ-ZMBH Alliance, German Cancer Research Center)

  • Francesca Tuorto

    (DKFZ-ZMBH Alliance, German Cancer Research Center
    Institute of Genetics and Biophysics ABT, CNR)

  • Günter Raddatz

    (DKFZ-ZMBH Alliance, German Cancer Research Center)

  • Tanja Musch

    (DKFZ-ZMBH Alliance, German Cancer Research Center)

  • Feng-Chun Yang

    (Herman B Wells Center for Pediatric Research, Indiana University Melvin and Bren Simon Cancer Center, Indiana University School of Medicine)

  • Mingjiang Xu

    (Herman B Wells Center for Pediatric Research, Indiana University Melvin and Bren Simon Cancer Center, Indiana University School of Medicine)

  • Frank Lyko

    (DKFZ-ZMBH Alliance, German Cancer Research Center)

  • Achim Breiling

    (DKFZ-ZMBH Alliance, German Cancer Research Center)

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.

Suggested Citation

  • Michael T. Bocker & Francesca Tuorto & Günter Raddatz & Tanja Musch & Feng-Chun Yang & Mingjiang Xu & Frank Lyko & Achim Breiling, 2012. "Hydroxylation of 5-methylcytosine by TET2 maintains the active state of the mammalian HOXA cluster," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
  • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1826
    DOI: 10.1038/ncomms1826
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    Cited by:

    1. Laure Talarmain & Matthew A. Clarke & David Shorthouse & Lilia Cabrera-Cosme & David G. Kent & Jasmin Fisher & Benjamin A. Hall, 2022. "HOXA9 has the hallmarks of a biological switch with implications in blood cancers," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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