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Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene

Nature volume 429, pages 571–574 (2004)Cite this article

Abstract

Transcription by RNA polymerase II in Saccharomyces cerevisiae and in humans is widespread, even in genomic regions that do not encode proteins1,2,3,4,5,6. The purpose of such intergenic transcription is largely unknown, although it can be regulatory7,8. We have discovered a role for one case of intergenic transcription by studying the S. cerevisiae SER3 gene. Our previous results demonstrated that transcription of SER3 is tightly repressed during growth in rich medium9. We now show that the regulatory region of this gene is highly transcribed under these conditions and produces a non-protein-coding RNA (SRG1). Expression of the SRG1 RNA is required for repression of SER3. Additional experiments have demonstrated that repression occurs by a transcription-interference mechanism in which SRG1 transcription across the SER3 promoter interferes with the binding of activators. This work identifies a previously unknown class of transcriptional regulatory genes.

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Figure 1: Evidence for active transcription 5′ of SER3.
Figure 2: Characterization of SRG1 transcription.
Figure 3: Tests of models for SRG1 function.
Figure 4: Two tests for transcription interference by SRG1.

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References

  1. Cawley, S. et al. Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 116, 499–509 (2004)

    Article  CAS  Google Scholar 

  2. Kapranov, P. et al. Large-scale transcriptional activity in chromosomes 21 and 22. Science 296, 916–919 (2002)

    Article  ADS  CAS  Google Scholar 

  3. Hurowitz, E. H. & Brown, P. O. Genome-wide analysis of mRNA lengths in Saccharomyces cerevisiae. Genome Biol. 5, R2 (2003)

    Article  Google Scholar 

  4. Rinn, J. L. et al. The transcriptional activity of human chromosome 22. Genes Dev. 17, 529–540 (2003)

    Article  CAS  Google Scholar 

  5. Saha, S. et al. Using the transcriptome to annotate the genome. Nature Biotechnol. 20, 508–512 (2002)

    Article  CAS  Google Scholar 

  6. Chen, J. et al. Identifying novel transcripts and novel genes in the human genome by using novel SAGE tags. Proc. Natl Acad. Sci. USA 99, 12257–12262 (2002)

    Article  ADS  CAS  Google Scholar 

  7. Gribnau, J., Diderich, K., Pruzina, S., Calzolari, R. & Fraser, P. Intergenic transcription and developmental remodeling of chromatin subdomains in the human β-globin locus. Mol. Cell 5, 377–386 (2000)

    Article  CAS  Google Scholar 

  8. Ashe, H. L., Monks, J., Wijgerde, M., Fraser, P. & Proudfoot, N. J. Intergenic transcription and transinduction of the human β-globin locus. Genes Dev. 11, 2494–2509 (1997)

    Article  CAS  Google Scholar 

  9. Martens, J. A. & Winston, F. Evidence that Swi/Snf directly represses transcription in S. cerevisiae. Genes Dev. 16, 2231–2236 (2002)

    Article  CAS  Google Scholar 

  10. Albers, E., Laize, V., Blomberg, A., Hohmann, S. & Gustafsson, L. Ser3p (Yer081wp) and Ser33p (Yil074cp) are phosphoglycerate dehydrogenases in Saccharomyces cerevisiae. J. Biol. Chem. 278, 10264–10272 (2003)

    Article  CAS  Google Scholar 

  11. Cliften, P. et al. Finding functional features in Saccharomyces genomes by phylogenetic footprinting. Science 301, 71–76 (2003)

    Article  ADS  CAS  Google Scholar 

  12. Kellis, M., Patterson, N., Endrizzi, M., Birren, B. & Lander, E. S. Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature 423, 241–254 (2003)

    Article  ADS  CAS  Google Scholar 

  13. van Hoof, A., Lennertz, P. & Parker, R. Yeast exosome mutants accumulate 3′-extended polyadenylated forms of U4 small nuclear RNA and small nucleolar RNAs. Mol. Cell. Biol. 20, 441–452 (2000)

    Article  CAS  Google Scholar 

  14. Andersen, A. A. & Panning, B. Epigenetic gene regulation by noncoding RNAs. Curr. Opin. Cell Biol. 15, 281–289 (2003)

    Article  CAS  Google Scholar 

  15. Hirschman, J. E., Durbin, K. J. & Winston, F. Genetic evidence for promoter competition in Saccharomyces cerevisiae. Mol. Cell. Biol. 8, 4608–4615 (1988)

    Article  CAS  Google Scholar 

  16. Emerman, M. & Temin, H. M. Genes with promoters in retrovirus vectors can be independently suppressed by an epigenetic mechanism. Cell 39, 449–467 (1984)

    Article  CAS  Google Scholar 

  17. Adhya, S. & Gottesman, M. Promoter occlusion: transcription through a promoter may inhibit its activity. Cell 29, 939–944 (1982)

    Article  CAS  Google Scholar 

  18. Corbin, V. & Maniatis, T. Role of transcriptional interference in the Drosophila melanogaster Adh promoter switch. Nature 337, 279–282 (1989)

    Article  ADS  CAS  Google Scholar 

  19. Cullen, B. R., Lomedico, P. T. & Ju, G. Transcriptional interference in avian retroviruses–implications for the promoter insertion model of leukaemogenesis. Nature 307, 241–245 (1984)

    Article  ADS  CAS  Google Scholar 

  20. Greger, I. H., Aranda, A. & Proudfoot, N. Balancing transcriptional interference and initiation on the GAL7 promoter of Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 97, 8415–8420 (2000)

    Article  ADS  CAS  Google Scholar 

  21. Hausler, B. & Somerville, R. L. Interaction in vivo between strong closely spaced constitutive promoters. J. Mol. Biol. 127, 353–356 (1979)

    Article  CAS  Google Scholar 

  22. Proudfoot, N. J. Transcriptional interference and termination between duplicated alpha-globin gene constructs suggests a novel mechanism for gene regulation. Nature 322, 562–565 (1986)

    Article  ADS  CAS  Google Scholar 

  23. Valerius, O., Brendel, C., Duvel, K. & Braus, G. H. Multiple factors prevent transcriptional interference at the yeast ARO4-HIS7 locus. J. Biol. Chem. 277, 21440–21445 (2002)

    Article  CAS  Google Scholar 

  24. Gottesman, S. Stealth regulation: biological circuits with small RNA switches. Genes Dev. 16, 2829–2842 (2002)

    Article  CAS  Google Scholar 

  25. Komarnitsky, P., Cho, E. J. & Buratowski, S. Different phosphorylated forms of RNA polymerase II and associated mRNA processing factors during transcription. Genes Dev. 14, 2452–2460 (2000)

    Article  CAS  Google Scholar 

  26. Dudley, A. M., Rougeulle, C. & Winston, F. The Spt components of SAGA facilitate TBP binding to a promoter at a post-activator-binding step in vivo. Genes Dev. 13, 2940–2945 (1999)

    Article  CAS  Google Scholar 

  27. Birse, C. E., Lee, B. A., Hansen, K. & Proudfoot, N. J. Transcriptional termination signals for RNA polymerase II in fission yeast. EMBO J. 16, 3633–3643 (1997)

    Article  CAS  Google Scholar 

  28. Duina, A. A. & Winston, F. Analysis of a mutant histone H3 that perturbs the association of Swi/Snf with chromatin. Mol. Cell. Biol. 24, 561–572 (2004)

    Article  CAS  Google Scholar 

  29. Hirschhorn, J. N., Brown, S. A., Clark, C. D. & Winston, F. Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure. Genes Dev. 6, 2288–2298 (1992)

    Article  CAS  Google Scholar 

  30. Dudley, A. M., Gansheroff, L. J. & Winston, F. Specific components of the SAGA complex are required for Gcn4- and Gcr1-mediated activation of the his4-912d promoter in Saccharomyces cerevisiae. Genetics 151, 1365–1378 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank A. Dudley, A. Duina and J. Wu for comments on the manuscript. We also thank P. Cliften, P. Sudarsanam and M. Johnston for sharing unpublished results, and J. O'Sullivan and N. Proudfoot for advice on transcription run-on experiments. This work was supported by a grant from the National Institutes of Health to F.W. and by a postdoctoral fellowship from the Canadian Institute for Health Research to J.A.M.

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Authors and Affiliations

  1. Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts, 02115, USA

    Joseph A. Martens, Lisa Laprade & Fred Winston

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  1. Joseph A. Martens
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  2. Lisa Laprade
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  3. Fred Winston
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Corresponding author

Correspondence to Fred Winston.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Table 1

List of S. cerevisiae strains used.

Supplementary Figure 1

Alignment of DNA sequence 5' of the SER3 gene of five related yeasts.

Supplementary Figure 2

Deletion analysis of the SER3 promoter region.

Supplementary Figure 3

Northern analysis of total and poly(A)-enriched RNA.

Supplementary Figure 4

Northern analysis of SRG1, SER3, and SNR190 (loading control) RNA levels in wild type and snf2Δ strains.

Supplementary Figure 5

Quantitation of the ChIP data shown in Figure 4.

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Martens, J., Laprade, L. & Winston, F. Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene. Nature 429, 571–574 (2004). https://doi.org/10.1038/nature02538

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