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.

  • Resource
  • Published:

Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae

Nature Structural & Molecular Biology volume 17, pages 251–257 (2010)Cite this article

Subjects

Abstract

Positioned nucleosomes limit the access of proteins to DNA and implement regulatory features encoded in eukaryotic genomes. Here we have generated the first genome-wide nucleosome positioning map for Schizosaccharomyces pombe and annotated transcription start and termination sites genome wide. Using this resource, we found surprising differences from the previously published nucleosome organization of the distantly related yeast Saccharomyces cerevisiae. DNA sequence guides nucleosome positioning differently: for example, poly(dA-dT) elements are not enriched in S. pombe nucleosome-depleted regions. Regular nucleosomal arrays emanate more asymmetrically—mainly codirectionally with transcription—from promoter nucleosome-depleted regions, but promoters harboring the histone variant H2A.Z also show regular arrays upstream of these regions. Regular nucleosome phasing in S. pombe has a very short repeat length of 154 base pairs and requires a remodeler, Mit1, that is conserved in humans but is not found in S. cerevisiae. Nucleosome positioning mechanisms are evidently not universal but evolutionarily plastic.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Alignment of genes at their TSS reveals a prominent NDR upstream and a regular nucleosomal array downstream of the TSS, with a shorter repeat length in S. pombe than in S. cerevisiae.
Figure 2: Subtypes of promoter chromatin organization are not generally predictive for levels of gene expression or RNA polymerase II occupancy.
Figure 3: Nucleosome occupancy responds differently to DNA sequence in S. pombe and S. cerevisiae.
Figure 4: Regular nucleosomal arrays emanate from promoter NDRs mostly codirectionally with transcription, with the exception of promoters enriched in H2A.Z.
Figure 5: The Snf2-type remodeler ATPase Mit1 is critical for the regularity of nucleosomal arrays.

Similar content being viewed by others

Accession codes

Accessions

Gene Expression Omnibus

References

  1. Jiang, C. & Pugh, B.F. Nucleosome positioning and gene regulation: advances through genomics. Nat. Rev. Genet. 10, 161–172 (2009).

    Article  CAS  Google Scholar 

  2. Radman-Livaja, M. & Rando, O.J. Nucleosome positioning: how is it established, and why does it matter? Dev. Biol. published online (13 June 2009).

  3. Segal, E. & Widom, J. What controls nucleosome positions? Trends Genet. 25, 335–343 (2009).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. 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 

  8. Field, Y. et al. Distinct modes of regulation by chromatin encoded through nucleosome positioning signals. PLOS Comput. Biol. 4, e1000216 (2008).

    Article  Google Scholar 

  9. Mavrich, T.N. et al. Nucleosome organization in the Drosophila genome. Nature 453, 358–362 (2008).

    Article  CAS  Google Scholar 

  10. Schones, D.E. et al. Dynamic regulation of nucleosome positioning in the human genome. Cell 132, 887–898 (2008).

    Article  CAS  Google Scholar 

  11. Valouev, A. et al. A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning. Genome Res. 18, 1051–1063 (2008).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  13. Field, Y. et al. Gene expression divergence in yeast is coupled to evolution of DNA-encoded nucleosome organization. Nat. Genet. 41, 438–445 (2009).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  16. Yuan, G.C. & Liu, J.S. Genomic sequence is highly predictive of local nucleosome depletion. PLOS Comput. Biol. 4, e13 (2008).

    Article  Google Scholar 

  17. Kaplan, N. et al. The DNA-encoded nucleosome organization of a eukaryotic genome. Nature 458, 362–366 (2009).

    Article  CAS  Google Scholar 

  18. Peckham, H.E. et al. Nucleosome positioning signals in genomic DNA. Genome Res. 17, 1170–1177 (2007).

    Article  CAS  Google Scholar 

  19. Badis, G. et al. A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Mol. Cell 32, 878–887 (2008).

    Article  CAS  Google Scholar 

  20. Parnell, T.J., Huff, J.T. & Cairns, B.R. RSC regulates nucleosome positioning at Pol II genes and density at Pol III genes. EMBO J. 27, 100–110 (2008).

    Article  CAS  Google Scholar 

  21. Gupta, S. et al. Predicting human nucleosome occupancy from primary sequence. PLOS Comput. Biol. 4, e1000134 (2008).

    Article  Google Scholar 

  22. Zhang, Y. et al. Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo. Nat. Struct. Mol. Biol. 16, 847–852 (2009).

    Article  CAS  Google Scholar 

  23. Hartley, P.D. & Madhani, H.D. Mechanisms that specify promoter nucleosome location and identity. Cell 137, 445–458 (2009).

    Article  CAS  Google Scholar 

  24. Drew, H.R. & Travers, A.A. DNA bending and its relation to nucleosome positioning. J. Mol. Biol. 186, 773–790 (1985).

    Article  CAS  Google Scholar 

  25. Sekinger, E.A., Moqtaderi, Z. & Struhl, K. Intrinsic histone-DNA interactions and low nucleosome density are important for preferential accessibility of promoter regions in yeast. Mol. Cell 18, 735–748 (2005).

    Article  CAS  Google Scholar 

  26. Wippo, C.J. et al. Differential cofactor requirements for histone eviction from two nucleosomes at the yeast PHO84 promoter are determined by intrinsic nucleosome stability. Mol. Cell. Biol. 29, 2960–2981 (2009).

    Article  CAS  Google Scholar 

  27. Korber, P. & Hörz, W. In vitro assembly of the characteristic chromatin organization at the yeast PHO5 promoter by a replication-independent extract system. J. Biol. Chem. 279, 35113–35120 (2004).

    Article  CAS  Google Scholar 

  28. Hertel, C.B., Langst, G., Hörz, W. & Korber, P. Nucleosome stability at the yeast PHO5 and PHO8 promoters correlates with differential cofactor requirements for chromatin opening. Mol. Cell. Biol. 25, 10755–10767 (2005).

    Article  CAS  Google Scholar 

  29. McManus, J. et al. Unusual chromosome structure of fission yeast DNA in mouse cells. J. Cell Sci. 107, 469–486 (1994).

    CAS  PubMed  Google Scholar 

  30. Bernardi, F., Zatchej, M. & Thoma, F. Species specific protein–DNA interactions may determine the chromatin units of genes in S. cerevisiae and in S. pombe. EMBO J. 11, 1177–1185 (1992).

    Article  CAS  Google Scholar 

  31. Lantermann, A., Stralfors, A., Fagerstrom-Billai, F., Korber, P. & Ekwall, K. Genome-wide mapping of nucleosome positions in Schizosaccharomyces pombe. Methods 48, 218–225 (2009).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  33. Godde, J.S. & Widom, J. Chromatin structure of Schizosaccharomyces pombe. A nucleosome repeat length that is shorter than the chromatosomal DNA length. J. Mol. Biol. 226, 1009–1025 (1992).

    Article  CAS  Google Scholar 

  34. Bernardi, F., Koller, T. & Thoma, F. The ade6 gene of the fission yeast Schizosaccharomyces pombe has the same chromatin structure in the chromosome and in plasmids. Yeast 7, 547–558 (1991).

    Article  CAS  Google Scholar 

  35. Thomas, J.O. & Furber, V. Yeast chromatin structure. FEBS Lett. 66, 274–280 (1976).

    Article  CAS  Google Scholar 

  36. Lee, C.K., Shibata, Y., Rao, B., Strahl, B.D. & Lieb, J.D. Evidence for nucleosome depletion at active regulatory regions genome-wide. Nat. Genet. 36, 900–905 (2004).

    Article  CAS  Google Scholar 

  37. Bernstein, B.E., Liu, C.L., Humphrey, E.L., Perlstein, E.O. & Schreiber, S.L. Global nucleosome occupancy in yeast. Genome Biol. 5, R62 (2004).

    Article  Google Scholar 

  38. Wirén, M. et al. Genomewide analysis of nucleosome density histone acetylation and HDAC function in fission yeast. EMBO J. 24, 2906–2918 (2005).

    Article  Google Scholar 

  39. Heichinger, C., Penkett, C.J., Bahler, J. & Nurse, P. Genome-wide characterization of fission yeast DNA replication origins. EMBO J. 25, 5171–5179 (2006).

    Article  CAS  Google Scholar 

  40. Fagerström-Billai, F., Durand-Dubief, M., Ekwall, K. & Wright, A.P. Individual subunits of the Ssn6-Tup11/12 corepressor are selectively required for repression of different target genes. Mol. Cell. Biol. 27, 1069–1082 (2007).

    Article  Google Scholar 

  41. Malavé, T.M. & Dent, S.Y. Transcriptional repression by Tup1-Ssn6. Biochem. Cell Biol. 84, 437–443 (2006).

    Article  Google Scholar 

  42. Ponomarenko, J.V. et al. Conformational and physicochemical DNA features specific for transcription factor binding sites. Bioinformatics 15, 654–668 (1999).

    Article  CAS  Google Scholar 

  43. Kornberg, R.D. & Stryer, L. Statistical distributions of nucleosomes: nonrandom locations by a stochastic mechanism. Nucleic Acids Res. 16, 6677–6690 (1988).

    Article  CAS  Google Scholar 

  44. 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 

  45. Buchanan, L. et al. The Schizosaccharomyces pombe Jmjc-protein, Msc1, prevents H2A.Z localization in centromeric and subtelomeric chromatin domains. PLoS Genet. 5, e1000726 (2009).

    Article  Google Scholar 

  46. Zofall, M. et al. Histone H2A.Z cooperates with RNAi and heterochromatin factors to suppress antisense RNAs. Nature 461, 419–422 (2009).

    Article  CAS  Google Scholar 

  47. Varga-Weisz, P.D. et al. Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase II. Nature 388, 598–602 (1997).

    Article  CAS  Google Scholar 

  48. 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 

  49. Sugiyama, T. et al. SHREC, an effector complex for heterochromatic transcriptional silencing. Cell 128, 491–504 (2007).

    Article  CAS  Google Scholar 

  50. Cam, H.P. et al. Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control of the fission yeast genome. Nat. Genet. 37, 809–819 (2005).

    Article  CAS  Google Scholar 

  51. Johnsson, A. et al. HAT-HDAC interplay modulates global histone H3K14 acetylation in gene-coding regions during stress. EMBO Rep. 10, 1009–1014 (2009).

    Article  CAS  Google Scholar 

  52. Svaren, J., Venter, U. & Hörz, W. In vivo analysis of nucleosome structure and transcription factor binding in Saccharomyces cerevisiae. Methods Mol. Genet. 6, 153–167 (1995).

    Article  CAS  Google Scholar 

  53. Huber, W., von Heydebreck, A., Sultmann, H., Poustka, A. & Vingron, M. Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 18 (Suppl. 1), S96–S104 (2002).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  56. Yuan, G.C. Targeted recruitment of histone modifications in humans predicted by genomic sequences. J. Comput. Biol. 16, 341–355 (2009).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank H. Bhuiyan and J. Walfridsson for generating the S. pombe expression data during their work in the group of K. Ekwall, R.R. Barrales (group of J.J. Ibeas, Universidad Pablo de Olavide, Sevilla, Spain) for bringing the first S. pombe strains into the Korber group, F. Thoma (ETH Zürich, Switzerland) for advice on chromatin analysis in S. pombe, F. Fagerström-Billai at the BEA microarray facility at Novum, Karolinska Institutet, for assistance, and F. Müller-Planitz (Adolf-Butenandt-Institut, Univ. Munich) for help with MATLAB. We are grateful for the communication of replication origin coordinates by C. Heichinger (Univ. Zürich) and of TSS coordinates by W. Lee (Stanford Univ.) and N. Dutrow (Univ. Utah). We thank H. Madhani and co-workers (Univ. California San Francisco) for sharing data before publication and for comments on the manuscript. This work was funded by the German Research Community (Transregio 5; P.K. and co-workers), the 6th Framework Programme of the European Union (NET programme; P.K. and K.E. and co-workers), the Swedish Cancer Society and Swedish Research Council (K.E. laboratory) and the Claudia Adams Barr Program (G.-C.Y.).

Author information

Author notes

  1. Alexandra B Lantermann and Tobias Straub: These authors contributed equally to this work.

Authors and Affiliations

  1. Adolf-Butenandt-Institut, University of Munich, Munich, Germany

    Alexandra B Lantermann, Tobias Straub & Philipp Korber

  2. Department of Biosciences and Nutrition, Karolinska Institutet, Center for Biosciences NOVUM, Huddinge, Sweden

    Annelie Strålfors & Karl Ekwall

  3. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA

    Guo-Cheng Yuan

  4. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    Guo-Cheng Yuan

Authors
  1. Alexandra B Lantermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tobias Straub
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Annelie Strålfors
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guo-Cheng Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karl Ekwall
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Philipp Korber
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.B.L. carried out all preparation and experimental analysis of biological material besides the actual microarray hybridizations, which were done at the BEA Affymetrix core facility at Novum with the help of A.S. A.B.L. did the S. pombe TSS and TTS annotation. T.S. did the bioinformatics analyses. G.-C.Y. provided the N-score codes, applied the model of Kaplan et al.17, analyzed DNA sequence features and gave advice on bioinformatics. A.S. and K.E. introduced A.B.L. to the work with S. pombe and microarrays. K.E. provided strains and reference data. P.K. and K.E. initiated, designed and supervised the study. A.B.L. and T.S. generated the figures. P.K. and A.B.L. wrote the paper. A.B.L. and T.S. contributed equally to the study. All authors discussed results and commented on the manuscript

Corresponding authors

Correspondence to Karl Ekwall or Philipp Korber.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7 and Supplementary Tables 1 and 4 (PDF 8759 kb)

Supplementary Table 2

Annotation of S. pombe transcription start sites (TSS) and transcription termination sites (TTS) (XLS 724 kb)

Supplementary Table 3

Parameters of the N-score models trained with S. cerevisiae or S. pombe experimental data (XLS 87 kb)

Supplementary Table 5

Genes with affected transcription levels in S. pombe mit1 mutant (XLS 61 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lantermann, A., Straub, T., Strålfors, A. et al. Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae. Nat Struct Mol Biol 17, 251–257 (2010). https://doi.org/10.1038/nsmb.1741

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsmb.1741

This article is cited by

Search

Advanced 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