Abstract
In the fission yeast S. pombe, the RNA interference (RNAi) pathway is required to generate small interfering RNAs (siRNAs) that mediate heterochromatic silencing of centromeric repeats. Here, we demonstrate that RNAi also functions to repress genomic elements other than constitutive heterochromatin. Using DNA adenine methyltransferase identification (DamID), we show that the RNAi proteins Dcr1 and Rdp1 physically associate with some euchromatic genes, noncoding RNA genes and retrotransposon long terminal repeats, and that this association is independent of the Clr4 histone methyltransferase. Physical association of RNAi with chromatin is sufficient to trigger a silencing response but not to assemble heterochromatin. The mode of silencing at the newly identified RNAi targets is consistent with a co-transcriptional gene silencing model, as proposed earlier, and functions with trace amounts of siRNAs. We anticipate that similar mechanisms could also be operational in other eukaryotes.
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Acknowledgements
We thank H. Grosshans, A. Peters, F. Mohn and all members of the Bühler lab for critical comments on the manuscript; A.H. Brand for plasmids; B. van Steensel for advice; and H.-R. Hotz for bioinformatics support. We also thank the genomics facility of the Friedrich Miescher Institute for Biomedical Research for array hybridizations. This work was supported by the Swiss National Science Foundation and the Novartis Research Foundation.
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K.J.W. and M.B. designed the research. K.J.W. designed and conducted experiments. D.G. wrote R scripts for data analysis. K.J.W. and D.G. analyzed the DamID data. T.P. conducted experiments. M.B. and K.J.W. analyzed the results and wrote the manuscript.
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Woolcock, K., Gaidatzis, D., Punga, T. et al. Dicer associates with chromatin to repress genome activity in Schizosaccharomyces pombe. Nat Struct Mol Biol 18, 94–99 (2011). https://doi.org/10.1038/nsmb.1935
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DOI: https://doi.org/10.1038/nsmb.1935
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