Resource | Published:

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

Nature Structural & Molecular Biology volume 17, pages 251257 (2010) | Download Citation


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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


Gene Expression Omnibus


  1. 1.

    & Nucleosome positioning and gene regulation: advances through genomics. Nat. Rev. Genet. 10, 161–172 (2009).

  2. 2.

    & Nucleosome positioning: how is it established, and why does it matter? Dev. Biol. published online (13 June 2009).

  3. 3.

    & What controls nucleosome positions? Trends Genet. 25, 335–343 (2009).

  4. 4.

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

  5. 5.

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

  6. 6.

    , , & Chromatin remodelling at promoters suppresses antisense transcription. Nature 450, 1031–1035 (2007).

  7. 7.

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

  8. 8.

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

  9. 9.

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

  10. 10.

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

  11. 11.

    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).

  12. 12.

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

  13. 13.

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

  14. 14.

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

  15. 15.

    , , & Nucleosome positions predicted through comparative genomics. Nat. Genet. 38, 1210–1215 (2006).

  16. 16.

    & Genomic sequence is highly predictive of local nucleosome depletion. PLOS Comput. Biol. 4, e13 (2008).

  17. 17.

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

  18. 18.

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

  19. 19.

    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).

  20. 20.

    , & RSC regulates nucleosome positioning at Pol II genes and density at Pol III genes. EMBO J. 27, 100–110 (2008).

  21. 21.

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

  22. 22.

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

  23. 23.

    & Mechanisms that specify promoter nucleosome location and identity. Cell 137, 445–458 (2009).

  24. 24.

    & DNA bending and its relation to nucleosome positioning. J. Mol. Biol. 186, 773–790 (1985).

  25. 25.

    , & Intrinsic histone-DNA interactions and low nucleosome density are important for preferential accessibility of promoter regions in yeast. Mol. Cell 18, 735–748 (2005).

  26. 26.

    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).

  27. 27.

    & 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).

  28. 28.

    , , & Nucleosome stability at the yeast PHO5 and PHO8 promoters correlates with differential cofactor requirements for chromatin opening. Mol. Cell. Biol. 25, 10755–10767 (2005).

  29. 29.

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

  30. 30.

    , & 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).

  31. 31.

    , , , & Genome-wide mapping of nucleosome positions in Schizosaccharomyces pombe. Methods 48, 218–225 (2009).

  32. 32.

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

  33. 33.

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

  34. 34.

    , & 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).

  35. 35.

    & Yeast chromatin structure. FEBS Lett. 66, 274–280 (1976).

  36. 36.

    , , , & Evidence for nucleosome depletion at active regulatory regions genome-wide. Nat. Genet. 36, 900–905 (2004).

  37. 37.

    , , , & Global nucleosome occupancy in yeast. Genome Biol. 5, R62 (2004).

  38. 38.

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

  39. 39.

    , , & Genome-wide characterization of fission yeast DNA replication origins. EMBO J. 25, 5171–5179 (2006).

  40. 40.

    , , & Individual subunits of the Ssn6-Tup11/12 corepressor are selectively required for repression of different target genes. Mol. Cell. Biol. 27, 1069–1082 (2007).

  41. 41.

    & Transcriptional repression by Tup1-Ssn6. Biochem. Cell Biol. 84, 437–443 (2006).

  42. 42.

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

  43. 43.

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

  44. 44.

    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).

  45. 45.

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

  46. 46.

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

  47. 47.

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

  48. 48.

    , , & Identification of multiple distinct Snf2 subfamilies with conserved structural motifs. Nucleic Acids Res. 34, 2887–2905 (2006).

  49. 49.

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

  50. 50.

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

  51. 51.

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

  52. 52.

    , & In vivo analysis of nucleosome structure and transcription factor binding in Saccharomyces cerevisiae. Methods Mol. Genet. 6, 153–167 (1995).

  53. 53.

    , , , & Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 18 (Suppl. 1), S96–S104 (2002).

  54. 54.

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

  55. 55.

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

  56. 56.

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

Download references


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

    • Alexandra B Lantermann
    •  & Tobias Straub

    These authors contributed equally to this work.


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

    • Alexandra B Lantermann
    • , Tobias Straub
    •  & Philipp Korber
  2. Karolinska Institutet, Department of Biosciences and Nutrition, 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


  1. Search for Alexandra B Lantermann in:

  2. Search for Tobias Straub in:

  3. Search for Annelie Strålfors in:

  4. Search for Guo-Cheng Yuan in:

  5. Search for Karl Ekwall in:

  6. Search for Philipp Korber in:


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

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Karl Ekwall or Philipp Korber.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–7 and Supplementary Tables 1 and 4

Excel files

  1. 1.

    Supplementary Table 2

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

  2. 2.

    Supplementary Table 3

    Parameters of the N-score models trained with S. cerevisiae or S. pombe experimental data

  3. 3.

    Supplementary Table 5

    Genes with affected transcription levels in S. pombe mit1 mutant

About this article

Publication history





Further reading