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5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming

Author

Listed:
  • Mark Wossidlo

    (Saarland University)

  • Toshinobu Nakamura

    (Medical School and Graduate School of Frontier Biosciences, Osaka University)

  • Konstantin Lepikhov

    (Saarland University)

  • C. Joana Marques

    (Laboratory of Developmental Genetics and Imprinting, The Babraham Institute)

  • Valeri Zakhartchenko

    (Ludwig-Maximilian University)

  • Michele Boiani

    (Max-Planck-Institut für molekulare Biomedizin)

  • Julia Arand

    (Saarland University)

  • Toru Nakano

    (Medical School and Graduate School of Frontier Biosciences, Osaka University)

  • Wolf Reik

    (Laboratory of Developmental Genetics and Imprinting, The Babraham Institute
    Centre for Trophoblast Research, University of Cambridge)

  • Jörn Walter

    (Saarland University)

Abstract

The epigenomes of early mammalian embryos are extensively reprogrammed to acquire a totipotent developmental potential. A major initial event in this reprogramming is the active loss/demethylation of 5-methylcytosine (5mC) in the zygote. Here, we report on findings that link this active demethylation to molecular mechanisms. We detect 5-hydroxymethylcytosine (5hmC) as a novel modification in mouse, bovine and rabbit zygotes. On zygotic development 5hmC accumulates in the paternal pronucleus along with a reduction of 5mC. A knockdown of the 5hmC generating dioxygenase Tet3 simultaneously affects the patterns of 5hmC and 5mC in the paternal pronucleus. This finding links the loss of 5mC to its conversion into 5hmC. The maternal pronucleus seems to be largely protected against this mechanism by PGC7/Dppa3/Stella, as in PGC7 knockout zygotes 5mC also becomes accessible to oxidation into 5hmC. In summary, our data suggest an important role of 5hmC and Tet3 for DNA methylation reprogramming processes in the mammalian zygote.

Suggested Citation

  • Mark Wossidlo & Toshinobu Nakamura & Konstantin Lepikhov & C. Joana Marques & Valeri Zakhartchenko & Michele Boiani & Julia Arand & Toru Nakano & Wolf Reik & Jörn Walter, 2011. "5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming," Nature Communications, Nature, vol. 2(1), pages 1-8, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1240
    DOI: 10.1038/ncomms1240
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    Cited by:

    1. Pascal Giehr & Charalampos Kyriakopoulos & Gabriella Ficz & Verena Wolf & Jörn Walter, 2016. "The Influence of Hydroxylation on Maintaining CpG Methylation Patterns: A Hidden Markov Model Approach," PLOS Computational Biology, Public Library of Science, vol. 12(5), pages 1-16, May.

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