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Dynamic link of DNA demethylation, DNA strand breaks and repair in mouse zygotes

MPG-Autoren
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Reinhardt,  Richard
High Throughput Technologies, Max Planck Institute for Molecular Genetics, Max Planck Society;

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Walter,  Jörn
Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Zitation

Wossidlo, M., Arand, J., Sebastiano, V., Lepikhov, K., Boiani, M., Reinhardt, R., et al. (2010). Dynamic link of DNA demethylation, DNA strand breaks and repair in mouse zygotes. EMBO Journal, 29(11), 1877-1888. doi:10.1038/emboj.2010.80.


Zitierlink: https://hdl.handle.net/11858/00-001M-0000-0010-7ADD-0
Zusammenfassung
In mammalian zygotes, the 5-methyl-cytosine (5mC) content of paternal chromosomes is rapidly changed by a yet unknown but presumably active enzymatic mechanism. Here, we describe the developmental dynamics and parental asymmetries of DNA methylation in relation to the presence of DNA strand breaks, DNA repair markers and a precise timing of zygotic DNA replication. The analysis shows that distinct pre-replicative (active) and replicative (active and passive) phases of DNA demethylation can be observed. These phases of DNA demethylation are concomitant with the appearance of DNA strand breaks and DNA repair markers such as γH2A.X and PARP-1, respectively. The same correlations are found in cloned embryos obtained after somatic cell nuclear transfer. Together, the data suggest that (1) DNA-methylation reprogramming is more complex and extended as anticipated earlier and (2) the DNA demethylation, particularly the rapid loss of 5mC in paternal DNA, is likely to be linked to DNA repair mechanisms.