Abstract
Transcription of eukaryotic genomes is more widespread than was previously anticipated and results in the production of many non–protein-coding RNAs (ncRNAs) whose functional relevance is poorly understood. Here we demonstrate that ncRNAs can counteract the encroachment of heterochromatin into neighboring euchromatin. We have identified a long ncRNA (termed BORDERLINE) that prevents spreading of the HP1 protein Swi6 and histone H3 Lys9 methylation beyond the pericentromeric repeat region of Schizosaccharomyces pombe chromosome 1. BORDERLINE RNAs act in a sequence-independent but locus-dependent manner and are processed by Dicer into short RNAs referred to as brdrRNAs. In contrast to canonical centromeric short interfering RNAs, brdrRNAs are rarely loaded onto Argonaute. Our analyses reveal an unexpected regulatory activity of ncRNAs in demarcating an epigenetically distinct chromosomal domain that could also be operational in other eukaryotes.
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25 September 2013
In the original article, the authors identified a long noncoding RNA, termed BORDERLINE, that prevents spreading of pericentromeric heterochromatin. In this addendum, they note that the BORDERLINE-encoding sequence partially overlaps with the previously described element IRC1-R.
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Acknowledgements
We are grateful to T. Roloff, K. Jacobeit, S. Dessus-Babus and D. Gaidatzis for help with Illumina deep sequencing, data processing and data analysis. This work was supported by funds to M.B. from the Swiss National Science Foundation (PP00P3_139204/1), the European Research Council (280410) and the European Molecular Biology Organization Young Investigator Programme (922.001). R.K.-S. was supported by a postdoctoral fellowship from the Peter and Traudl Engelhorn Foundation. The Friedrich Miescher Institute for Biomedical Research is supported by the Novartis Research Foundation.
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R.K.-S., C.K. and Y.S. performed ChIP experiments. R.K.-S. prepared libraries for ChIP-seq and analyzed the data and performed RACE experiments. C.K. created strains, performed Northern blotting and quantitative real-time PCR and prepared RNA for small-RNA deep sequencing. H.-R.H. conducted bioinformatic analysis of small-RNA deep-sequencing data. M.B., C.K. and R.K.-S. designed the study, analyzed the data and wrote the manuscript.
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Keller, C., Kulasegaran-Shylini, R., Shimada, Y. et al. Noncoding RNAs prevent spreading of a repressive histone mark. Nat Struct Mol Biol 20, 994–1000 (2013). https://doi.org/10.1038/nsmb.2619
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DOI: https://doi.org/10.1038/nsmb.2619
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