Recent transcriptome analyses using high-density tiling arrays1,2,3 and data from large-scale analyses of full-length complementary DNA libraries by the FANTOM3 consortium4,5 demonstrate that many transcripts are non-coding RNAs (ncRNAs). These transcriptome analyses indicate that many of the non-coding regions, previously thought to be functionally inert, are actually transcriptionally active regions with various features. Furthermore, most relatively large (∼several kilobases) polyadenylated messenger RNA transcripts are transcribed from regions harbouring little coding potential. However, the function of such ncRNAs is mostly unknown and has been a matter of debate2. Here we show that RNA polymerase II (RNAPII) transcription of ncRNAs is required for chromatin remodelling at the fission yeast Schizosaccharomyces pombe fbp1+ locus during transcriptional activation. The chromatin at fbp1+ is progressively converted to an open configuration, as several species of ncRNAs are transcribed through fbp1+. This is coupled with the translocation of RNAPII through the region upstream of the eventual fbp1+ transcriptional start site. Insertion of a transcription terminator into this upstream region abolishes both the cascade of transcription of ncRNAs and the progressive chromatin alteration. Our results demonstrate that transcription through the promoter region is required to make DNA sequences accessible to transcriptional activators and to RNAPII.
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We thank W. Lin for critically reading this manuscript. This work was supported by grants-in-aid for scientific research in a priority area, the Ministry of Education, Culture, Sports, Science and Technology, Japan.
Author Contributions K.H. and K.O. conceived the project. K.H. planned, performed and analysed most of the experiments. T.M. performed Rst2-ChIP and RACE experiments. T.M. and K.K. performed the genome tiling array experiment. K.H. wrote most of the paper. C.S.H., T.S. and K.O. gave scientific advice and financial support. K.O. supervised the project.
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Hirota, K., Miyoshi, T., Kugou, K. et al. Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs. Nature 456, 130–134 (2008) doi:10.1038/nature07348
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