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Chromatin remodelling at promoters suppresses antisense transcription

Nature volume 450, pages 1031–1035 (2007)Cite this article

Abstract

Chromatin allows the eukaryotic cell to package its DNA efficiently. To understand how chromatin structure is controlled across the Saccharomyces cerevisiae genome, we have investigated the role of the ATP-dependent chromatin remodelling complex Isw2 in positioning nucleosomes. We find that Isw2 functions adjacent to promoter regions where it repositions nucleosomes at the interface between genic and intergenic sequences. Nucleosome repositioning by Isw2 is directional and results in increased nucleosome occupancy of the intergenic region. Loss of Isw2 activity leads to inappropriate transcription, resulting in the generation of both coding and noncoding transcripts. Here we show that Isw2 repositions nucleosomes to enforce directionality on transcription by preventing transcription initiation from cryptic sites. Our analyses reveal how chromatin is organized on a global scale and advance our understanding of how transcription is regulated.

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Figure 1: Definition of Isw2 function using high-density microarrays.
Figure 2: Distinct nucleosome organization at the 5′ end of genes.
Figure 3: Loss of Isw2 leads to directional nucleosome repositioning at the 5′ end and 3′ end of genes.
Figure 4: Loss of Isw2 leads to noncoding transcription at the 3′ end of genes.

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Accession codes

Primary accessions

Gene Expression Omnibus

Data deposits

Raw data are deposited at GEO with accession numbers GSE8813, GSE8814 and GSE8815.

References

  1. Luger, K., Mader, A. W., Richmond, R. K., Sargent, D. F. & Richmond, T. J. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389, 251–260 (1997)

    Article  CAS  ADS  Google Scholar 

  2. Ehrenhofer-Murray, A. E. Chromatin dynamics at DNA replication, transcription and repair. Eur. J. Biochem. 271, 2335–2349 (2004)

    Article  CAS  Google Scholar 

  3. Satchwell, S. C., Drew, H. R. & Travers, A. A. Sequence periodicities in chicken nucleosome core DNA. J. Mol. Biol. 191, 659–675 (1986)

    Article  CAS  Google Scholar 

  4. Lowary, P. T. & Widom, J. New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning. J. Mol. Biol. 276, 19–42 (1998)

    Article  CAS  Google Scholar 

  5. Anderson, J. D. & Widom, J. Poly(dA-dT) promoter elements increase the equilibrium accessibility of nucleosomal DNA target sites. Mol. Cell. Biol. 21, 3830–3839 (2001)

    Article  CAS  Google Scholar 

  6. Segal, E. et al. A genomic code for nucleosome positioning. Nature 442, 772–778 (2006)

    Article  CAS  ADS  Google Scholar 

  7. Ioshikhes, I. P., Albert, I., Zanton, S. J. & Pugh, B. F. Nucleosome positions predicted through comparative genomics. Nature Genet. 38, 1210–1215 (2006)

    Article  CAS  Google Scholar 

  8. Narlikar, G. J., Fan, H. Y. & Kingston, R. E. Cooperation between complexes that regulate chromatin structure and transcription. Cell 108, 475–487 (2002)

    Article  CAS  Google Scholar 

  9. Rando, O. J. & Ahmad, K. Rules and regulation in the primary structure of chromatin. Curr. Opin. Cell Biol. 19, 250–256 (2007)

    Article  CAS  Google Scholar 

  10. Eisen, J. A., Sweder, K. S. & Hanawalt, P. C. Evolution of the SNF2 family of proteins: subfamilies with distinct sequences and functions. Nucleic Acids Res. 23, 2715–2723 (1995)

    Article  CAS  Google Scholar 

  11. Flaus, A., Martin, D. M., Barton, G. J. & Owen-Hughes, T. Identification of multiple distinct Snf2 subfamilies with conserved structural motifs. Nucleic Acids Res. 34, 2887–2905 (2006)

    Article  CAS  Google Scholar 

  12. Badenhorst, P., Voas, M., Rebay, I. & Wu, C. Biological functions of the ISWI chromatin remodeling complex NURF. Genes Dev. 16, 3186–3198 (2002)

    Article  CAS  Google Scholar 

  13. Yasui, D., Miyano, M., Cai, S., Varga-Weisz, P. & Kohwi-Shigematsu, T. SATB1 targets chromatin remodelling to regulate genes over long distances. Nature 419, 641–645 (2002)

    Article  CAS  ADS  Google Scholar 

  14. Deuring, R. et al. The ISWI chromatin-remodeling protein is required for gene expression and the maintenance of higher order chromatin structure in vivo . Mol. Cell 5, 355–365 (2000)

    Article  CAS  Google Scholar 

  15. Collins, N. et al. An ACF1–ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin. Nature Genet. 32, 627–632 (2002)

    Article  CAS  Google Scholar 

  16. Poot, R. A. et al. The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci. Nature Cell Biol. 6, 1236–1244 (2004)

    Article  CAS  Google Scholar 

  17. Fyodorov, D. V., Blower, M. D., Karpen, G. H. & Kadonaga, J. T. Acf1 confers unique activities to ACF/CHRAC and promotes the formation rather than disruption of chromatin in vivo . Genes Dev. 18, 170–183 (2004)

    Article  CAS  Google Scholar 

  18. Zhou, Y., Santoro, R. & Grummt, I. The chromatin remodeling complex NoRC targets HDAC1 to the ribosomal gene promoter and represses RNA polymerase I transcription. EMBO J. 21, 4632–4640 (2002)

    Article  CAS  Google Scholar 

  19. Li, J., Langst, G. & Grummt, I. NoRC-dependent nucleosome positioning silences rRNA genes. EMBO J. 25, 5735–5741 (2006)

    Article  CAS  Google Scholar 

  20. Hakimi, M. A. et al. A chromatin remodelling complex that loads cohesin onto human chromosomes. Nature 418, 994–998 (2002)

    Article  CAS  ADS  Google Scholar 

  21. Goldmark, J. P., Fazzio, T. G., Estep, P. W., Church, G. M. & Tsukiyama, T. The Isw2 chromatin remodeling complex represses early meiotic genes upon recruitment by Ume6p. Cell 103, 423–433 (2000)

    Article  CAS  Google Scholar 

  22. Fazzio, T. G., Gelbart, M. E. & Tsukiyama, T. Two distinct mechanisms of chromatin interaction by the isw2 chromatin remodeling complex in vivo . Mol. Cell. Biol. 25, 9165–9174 (2005)

    Article  CAS  Google Scholar 

  23. Kent, N. A., Karabetsou, N., Politis, P. K. & Mellor, J. In vivo chromatin remodeling by yeast ISWI homologs Isw1p and Isw2p. Genes Dev. 15, 619–626 (2001)

    Article  CAS  Google Scholar 

  24. Whitehouse, I. & Tsukiyama, T. Antagonistic forces that position nucleosomes in vivo . Nature Struct. Mol. Biol. 13, 633–640 (2006)

    Article  CAS  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

  26. Gelbart, M. E., Bachman, N., Delrow, J., Boeke, J. D. & Tsukiyama, T. Genome-wide identification of Isw2 chromatin-remodeling targets by localization of a catalytically inactive mutant. Genes Dev. 19, 942–954 (2005)

    Article  CAS  Google Scholar 

  27. Fazzio, T. G. et al. Widespread collaboration of Isw2 and Sin3–Rpd3 chromatin remodeling complexes in transcriptional repression. Mol. Cell. Biol. 21, 6450–6460 (2001)

    Article  CAS  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

  29. Houseley, J., LaCava, J. & Tollervey, D. RNA-quality control by the exosome. Nature Rev. Mol. Cell Biol. 7, 529–539 (2006)

    Article  CAS  Google Scholar 

  30. 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)

    Article  CAS  Google Scholar 

  31. LaCava, J. et al. RNA degradation by the exosome is promoted by a nuclear polyadenylation complex. Cell 121, 713–724 (2005)

    Article  CAS  Google Scholar 

  32. Vanacova, S. et al. A new yeast poly(A) polymerase complex involved in RNA quality control. PLoS Biol. 3, e189 (2005)

    Article  Google Scholar 

  33. 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)

    Article  CAS  ADS  Google Scholar 

  34. Egecioglu, D. E., Henras, A. K. & Chanfreau, G. F. Contributions of Trf4p- and Trf5p-dependent polyadenylation to the processing and degradative functions of the yeast nuclear exosome. RNA 12, 26–32 (2006)

    Article  CAS  Google Scholar 

  35. Pan, X. et al. A DNA integrity network in the yeast Saccharomyces cerevisiae . Cell 124, 1069–1081 (2006)

    Article  CAS  Google Scholar 

  36. Behe, M. J. An overabundance of long oligopurine tracts occurs in the genome of simple and complex eukaryotes. Nucleic Acids Res. 23, 689–695 (1995)

    Article  CAS  Google Scholar 

  37. Kunkel, G. R. & Martinson, H. G. Nucleosomes will not form on double-stranded RNa or over poly(dA).poly(dT) tracts in recombinant DNA. Nucleic Acids Res. 9, 6869–6888 (1981)

    Article  CAS  Google Scholar 

  38. Iyer, V. & Struhl, K. Poly(dA:dT), a ubiquitous promoter element that stimulates transcription via its intrinsic DNA structure. EMBO J. 14, 2570–2579 (1995)

    Article  CAS  Google Scholar 

  39. Raisner, R. M. et al. Histone variant H2A.Z marks the 5′ ends of both active and inactive genes in euchromatin. Cell 123, 233–248 (2005)

    Article  CAS  Google Scholar 

  40. Guillemette, B. et al. Variant histone H2A.Z is globally localized to the promoters of inactive yeast genes and regulates nucleosome positioning. PLoS Biol. 3, e384 (2005)

    Article  Google Scholar 

  41. Zhang, H., Roberts, D. N. & Cairns, B. R. Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cell 123, 219–231 (2005)

    Article  CAS  Google Scholar 

  42. Brickner, D. G. et al. H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state. PLoS Biol. 5, e81 (2007)

    Article  Google Scholar 

  43. Dion, M. F. et al. Dynamics of replication-independent histone turnover in budding yeast. Science 315, 1405–1408 (2007)

    Article  CAS  ADS  Google Scholar 

  44. Eisen, M. B., Spellman, P. T., Brown, P. O. & Botstein, D. Cluster analysis and display of genome-wide expression patterns. Proc. Natl Acad. Sci. USA 95, 14863–14868 (1998)

    Article  CAS  ADS  Google Scholar 

  45. Liu, C. L. et al. Single-nucleosome mapping of histone modifications in S. cerevisiae . PLoS Biol. 3, e328 (2005)

    Article  Google Scholar 

  46. Zhang, Z. & Dietrich, F. S. Mapping of transcription start sites in Saccharomyces cerevisiae using 5′ SAGE. Nucleic Acids Res. 33, 2838–2851 (2005)

    Article  CAS  Google Scholar 

  47. MacIsaac, K. D. et al. An improved map of conserved regulatory sites for Saccharomyces cerevisiae . BMC Bioinformatics 7, 113 (2006)

    Article  Google Scholar 

  48. Miura, F. et al. A large-scale full-length cDNA analysis to explore the budding yeast transcriptome. Proc. Natl Acad. Sci. USA 103, 17846–17851 (2006)

    Article  CAS  ADS  Google Scholar 

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Acknowledgements

We thank members of the Tsukiyama and Henikoff laboratories for discussions, R. Basom for help with data analysis, and S. Henikoff, S. Biggins, S. Hahn and T. Owen-Hughes for critical reading of the manuscript. This work was supported by funds from NIGMS and the Leukemia and Lymphoma Society to T.T, from the Burroughs Wellcome Fund and Human Frontier Science Program to O.J.R, and from the NCI to J.D.

Author Contributions Experimental strategy was designed by I.W. and T.T., and experiments were performed by I.W. Preliminary nucleosome mapping was performed in collaboration with O.J.R. Data were analysed by I.W., with technical assistance from J.D. The paper was written by I.W., with assistance from T.T. All authors discussed the results and experiments, and edited the manuscript.

Author information

Authors and Affiliations

  1. Division of Basic Sciences,,

    Iestyn Whitehouse & Toshio Tsukiyama

  2. Genomics Resource, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA ,

    Jeff Delrow

  3. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA,

    Oliver J. Rando

Authors
  1. Iestyn Whitehouse
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  2. Oliver J. Rando
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Corresponding author

Correspondence to Toshio Tsukiyama.

Supplementary information

Supplementary Information

This file contains Supplementary Table S1and Supplementary Figures S1-S18 with Legends. (PDF 4886 kb)

Supplementary Table

This file contains Supplementary Table with summary data of regions bound by Isw2, sites of chromatin remodelling and lists of nucleosome positions. (XLS 25913 kb)

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Whitehouse, I., Rando, O., Delrow, J. et al. Chromatin remodelling at promoters suppresses antisense transcription. Nature 450, 1031–1035 (2007). https://doi.org/10.1038/nature06391

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