Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Bidirectional promoters generate pervasive transcription in yeast

Abstract

Genome-wide pervasive transcription has been reported in many eukaryotic organisms1,2,3,4,5,6,7, revealing a highly interleaved transcriptome organization that involves hundreds of previously unknown non-coding RNAs8. These recently identified transcripts either exist stably in cells (stable unannotated transcripts, SUTs) or are rapidly degraded by the RNA surveillance pathway (cryptic unstable transcripts, CUTs). One characteristic of pervasive transcription is the extensive overlap of SUTs and CUTs with previously annotated features, which prompts questions regarding how these transcripts are generated, and whether they exert function9. Single-gene studies have shown that transcription of SUTs and CUTs can be functional, through mechanisms involving the generated RNAs10,11 or their generation itself12,13,14. So far, a complete transcriptome architecture including SUTs and CUTs has not been described in any organism. Knowledge about the position and genome-wide arrangement of these transcripts will be instrumental in understanding their function8,15. Here we provide a comprehensive analysis of these transcripts in the context of multiple conditions, a mutant of the exosome machinery and different strain backgrounds of Saccharomyces cerevisiae. We show that both SUTs and CUTs display distinct patterns of distribution at specific locations. Most of the newly identified transcripts initiate from nucleosome-free regions (NFRs) associated with the promoters of other transcripts (mostly protein-coding genes), or from NFRs at the 3′ ends of protein-coding genes. Likewise, about half of all coding transcripts initiate from NFRs associated with promoters of other transcripts. These data change our view of how a genome is transcribed, indicating that bidirectionality is an inherent feature of promoters. Such an arrangement of divergent and overlapping transcripts may provide a mechanism for local spreading of regulatory signals—that is, coupling the transcriptional regulation of neighbouring genes by means of transcriptional interference or histone modification.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Transcript maps.
Figure 2: Properties of divergent transcript pairs.
Figure 3: 5′ and 3′ NFR sharing.

Accession codes

Primary accessions

ArrayExpress

Data deposits

Raw data are available from ArrayExpress (http://www.ebi.ac.uk/arrayexpress) under accession number E-TABM-590.

References

  1. 1

    Bertone, P. et al. Global identification of human transcribed sequences with genome tiling arrays. Science 306, 2242–2246 (2004)

    ADS  CAS  Article  Google Scholar 

  2. 2

    Carninci, P. et al. The transcriptional landscape of the mammalian genome. Science 309, 1559–1563 (2005)

    ADS  CAS  Article  Google Scholar 

  3. 3

    David, L. et al. A high-resolution map of transcription in the yeast genome. Proc. Natl Acad. Sci. USA 103, 5320–5325 (2006)

    ADS  CAS  Article  Google Scholar 

  4. 4

    Dutrow, N. et al. Dynamic transcriptome of Schizosaccharomyces pombe shown by RNA–DNA hybrid mapping. Nature Genet. 40, 977–986 (2008)

    CAS  Article  Google Scholar 

  5. 5

    Li, L. et al. Genome-wide transcription analyses in rice using tiling microarrays. Nature Genet. 38, 124–129 (2006)

    CAS  Article  Google Scholar 

  6. 6

    Stolc, V. et al. A gene expression map for the euchromatic genome of Drosophila melanogaster . Science 306, 655–660 (2004)

    ADS  CAS  Article  Google Scholar 

  7. 7

    Wilhelm, B. T. et al. Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution. Nature 453, 1239–1243 (2008)

    ADS  CAS  Article  Google Scholar 

  8. 8

    Kapranov, P., Willingham, A. T. & Gingeras, T. R. Genome-wide transcription and the implications for genomic organization. Nature Rev. Genet. 8, 413–423 (2007)

    CAS  Article  Google Scholar 

  9. 9

    Struhl, K. Transcriptional noise and the fidelity of initiation by RNA polymerase II. Nature Struct. Mol. Biol. 14, 103–105 (2007)

    CAS  Article  Google Scholar 

  10. 10

    Berretta, J., Pinskaya, M. & Morillon, A. A cryptic unstable transcript mediates transcriptional trans-silencing of the Ty1 retrotransposon in S. cerevisiae . Genes Dev. 22, 615–626 (2008)

    CAS  Article  Google Scholar 

  11. 11

    Camblong, J. et al. Antisense RNA stabilization induces transcriptional gene silencing via histone deacetylation in S. cerevisiae . Cell 131, 706–717 (2007)

    CAS  Article  Google Scholar 

  12. 12

    Bird, A. J., Gordon, M., Eide, D. J. & Winge, D. R. Repression of ADH1 and ADH3 during zinc deficiency by Zap1-induced intergenic RNA transcripts. EMBO J. 25, 5726–5734 (2006)

    CAS  Article  Google Scholar 

  13. 13

    Hongay, C. F., Grisafi, P. L., Galitski, T. & Fink, G. R. Antisense transcription controls cell fate in Saccharomyces cerevisiae . Cell 127, 735–745 (2006)

    CAS  Article  Google Scholar 

  14. 14

    Martens, J. A., Laprade, L. & Winston, F. Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene. Nature 429, 571–574 (2004)

    ADS  CAS  Article  Google Scholar 

  15. 15

    Birney, E. et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799–816 (2007)

    ADS  CAS  Article  Google Scholar 

  16. 16

    Huber, W., Toedling, J. & Steinmetz, L. M. Transcript mapping with high-density oligonucleotide tiling arrays. Bioinformatics 22, 1963–1970 (2006)

    CAS  Article  Google Scholar 

  17. 17

    Davis, C. A. & Ares, M. Accumulation of unstable promoter-associated transcripts upon loss of the nuclear exosome subunit Rrp6p in Saccharomyces cerevisiae . Proc. Natl Acad. Sci. USA 103, 3262–3267 (2006)

    ADS  CAS  Article  Google Scholar 

  18. 18

    Wyers, F. et al. Cryptic pol II transcripts are degraded by a nuclear quality control pathway involving a new poly(A) polymerase. Cell 121, 725–737 (2005)

    CAS  Article  Google Scholar 

  19. 19

    Nagalakshmi, U. et al. The transcriptional landscape of the yeast genome defined by RNA sequencing. Science 320, 1344–1349 (2008)

    ADS  CAS  Article  Google Scholar 

  20. 20

    Lee, W. et al. A high-resolution atlas of nucleosome occupancy in yeast. Nature Genet. 39, 1235–1244 (2007)

    CAS  Article  Google Scholar 

  21. 21

    Shivaswamy, S. et al. Dynamic remodeling of individual nucleosomes across a eukaryotic genome in response to transcriptional perturbation. PLoS Biol. 6, e65 (2008)

    Article  Google Scholar 

  22. 22

    Mavrich, T. N. et al. A barrier nucleosome model for statistical positioning of nucleosomes throughout the yeast genome. Genome Res. 18, 1073–1083 (2008)

    CAS  Article  Google Scholar 

  23. 23

    Whitehouse, I., Rando, O. J., Delrow, J. & Tsukiyama, T. Chromatin remodelling at promoters suppresses antisense transcription. Nature 450, 1031–1035 (2007)

    ADS  CAS  Article  Google Scholar 

  24. 24

    Yuan, G. C. et al. Genome-scale identification of nucleosome positions in S. cerevisiae . Science 309, 626–630 (2005)

    ADS  CAS  Article  Google Scholar 

  25. 25

    Albert, I. et al. Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome. Nature 446, 572–576 (2007)

    ADS  CAS  Article  Google Scholar 

  26. 26

    Hermsen, R., ten Wolde, P. R. & Teichmann, S. Chance and necessity in chromosomal gene distributions. Trends Genet. 24, 216–219 (2008)

    CAS  Article  Google Scholar 

  27. 27

    Uhler, J. P., Hertel, C. & Svejstrup, J. Q. A role for noncoding transcription in activation of the yeast PHO5 gene. Proc. Natl Acad. Sci. USA 104, 8011–8016 (2007)

    ADS  CAS  Article  Google Scholar 

  28. 28

    Wei, W. et al. Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789. Proc. Natl Acad. Sci. USA 104, 12825–12830 (2007)

    ADS  CAS  Article  Google Scholar 

  29. 29

    Teodorovic, S., Walls, C. D. & Elmendorf, H. G. Bidirectional transcription is an inherent feature of Giardia lamblia promoters and contributes to an abundance of sterile antisense transcripts throughout the genome. Nucleic Acids Res. 35, 2544–2553 (2007)

    CAS  Article  Google Scholar 

  30. 30

    Perocchi, F., Xu, Z., Clauder-Münster, S. & Steinmetz, L. M. Antisense artifacts in transcriptome microarray experiments are resolved by actinomycin D. Nucleic Acids Res. 35, e128 (2007)

    Article  Google Scholar 

Download references

Acknowledgements

We thank A. Akhtar, A. Ladurner, S. Blandin, R. Aiyar, E. Mancera and E. Fritsch for comments on the manuscript, J. Toedling for discussion and for the template of the website, C. Girardot for data submission to ArrayExpress, N. Proudfoot for access to experimental equipment, and the contributors to the Bioconductor (http://www.bioconductor.org) and R (http://www.r-project.org) projects for their software. This work was supported by grants to L.M.S. from the National Institutes of Health and Deutsche Forschungsgemeinschaft, by a SystemsX fellowship to E.G., by a Roche fellowship to J.C. and by grants to F.S. from SNF and NCCR Frontiers in Genetics.

Author Contributions L.M.S., Z.X. and W.W. designed the research; Z.X. and W.W. annotated the transcripts with the help of J.G. and F.P.; W.W. and Z.X. performed analysis of the transcripts with the help of J.G.; F.P. and S.C.-M. performed the array hybridizations; J.C. E.G. and F.S. provided samples for the rrp6Δ mutant, and designed and performed validation polymerase chain reaction with reverse transcription and 5′ RACE experiments; L.M.S., J.G., F.S. and W.H. supervised the research; and L.M.S., Z.X., W.W., J.G. and W.H. wrote the manuscript.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Lars M. Steinmetz.

Supplementary information

Supplementary Information

This file contains Supplementary Data, Supplementary Methods, Supplementary Tables 1, 2, 4, and 7-10, Supplementary References and Supplementary Figures 1-5 with Legends, (see separate files s2-s7 for Supplementary Tables 3, 5, 6 and 11-13). (PDF 430 kb)

Supplementary Table 3

Supplementary Table 3: Transcript boundaries for ORF-Ts, SUTs and CUTs (XLS 1600 kb)

Supplementary Table 5

Supplementary Table 5: Primers used in this study, RT-PCR and 5’ RACE results (XLS 53 kb)

Supplementary Table 6

Supplementary Table 6: List of SUTs with at least 2 fold increase in rrp6Δ vs. WT. (XLS 27 kb)

Supplementary Table 11

Supplementary Table 11: Transcripts initiating from shared NFRs (XLS 422 kb)

Supplementary Table 12

Supplementary Table 12: List of 19 examples like GAL80-SUR7 (XLS 25 kb)

Supplementary Table 13

Supplementary Table 13: Expression level of transcript pairs containing SUTs (XLS 169 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Xu, Z., Wei, W., Gagneur, J. et al. Bidirectional promoters generate pervasive transcription in yeast. Nature 457, 1033–1037 (2009). https://doi.org/10.1038/nature07728

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing