Abstract
Here we show that the cytosine-5 methyltransferase DNMT2 controls retrotransposon silencing in Drosophila somatic cells. In Drosophila, significant DNMT2-dependent DNA methylation occurs during early embryogenesis. Suppression of white gene silencing by Mt2 (Dnmt2) null mutations in variegated P[w+] element insertions identified functional targets of DNMT2. The enzyme controls DNA methylation at retrotransposons in early embryos and initiates histone H4K20 trimethylation catalyzed by the SUV4-20 methyltransferase. In somatic cells, loss of DNMT2 eliminates H4K20 trimethylation at retrotransposons and impairs maintenance of retrotransposon silencing. In Dnmt2 and Suv4-20 null genotypes, retrotransposons are strongly overexpressed in somatic but not germline cells, where retrotransposon silencing depends on an RNAi mechanism. DNMT2 also controls integrity of chromosome 2R and 3R telomeres. In Dnmt2 null strains, we found stable loss of the subtelomeric clusters of defective Invader4 elements. Together, these results demonstrate a previously unappreciated role of DNA methylation in retrotransposon silencing and telomere integrity in Drosophila.
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27 October 2010
In the version of this article initially published, the Methods didn't cite the source of the w1118 strain used as wild-type control. The authors used a newly established w1118 isogenic strain and the origin of the strain is described in reference 20. The error has been corrected in the HTML and PDF versions of the article.
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Acknowledgements
We thank M. Kube, M. Klimm and K. Kittlaus for experimental support, F. Lyko (Deutsches Krebsforschungszentrum) for providing a DNMT2-specific antibody, S.C.R. Elgin (Washington University, St. Louis) for HP1 antibody, T. Jenuwein (Max-Planck Institute of Immunobiology) for H4K20me3 antibody and Fermentas for providing SgeI enzyme and sharing the quality control data (Supplementary Fig. 1). This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG Priority Programme Epigenetics) and the European Union (EU-network epigenome).
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G.R. conceived and designed the experiments and contributed to genetic analysis. S.P., O.N., D.W., F.H. and M.C.O. carried out genetic, molecular and immunocytological analysis. G.R. and S.P. analyzed the data and wrote the paper.
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Supplementary Figures 1–10, Supplementary Tables 1 and 2 and Supplementary Methods (PDF 1449 kb)
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Phalke, S., Nickel, O., Walluscheck, D. et al. Retrotransposon silencing and telomere integrity in somatic cells of Drosophila depends on the cytosine-5 methyltransferase DNMT2. Nat Genet 41, 696–702 (2009). https://doi.org/10.1038/ng.360
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DOI: https://doi.org/10.1038/ng.360
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