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Nucleosome positions predicted through comparative genomics

Nature Genetics volume 38, pages 12101215 (2006) | Download Citation



DNA sequence has long been recognized as an important contributor to nucleosome positioning, which has the potential to regulate access to genes. The extent to which the nucleosomal architecture at promoters is delineated by the underlying sequence is now being worked out. Here we use comparative genomics to report a genome-wide map of nucleosome positioning sequences (NPSs) located in the vicinity of all Saccharomyces cerevisiae genes. We find that the underlying DNA sequence provides a very good predictor of nucleosome locations that have been experimentally mapped to a small fraction of the genome. Notably, distinct classes of genes possess characteristic arrangements of NPSs that may be important for their regulation. In particular, genes that have a relatively compact NPS arrangement over the promoter region tend to have a TATA box buried in an NPS and tend to be highly regulated by chromatin modifying and remodeling factors.

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  1. 1.

    & The structure of DNA in the nucleosome core. Nature 423, 145–150 (2003).

  2. 2.

    , , , & Nucleosome DNA sequence pattern revealed by multiplea alignment of experimentally mapped sequences. J. Mol. Biol. 262, 129–139 (1996).

  3. 3.

    , & Sequence periodicities in chicken nucleosome core DNA. J. Mol. Biol. 191, 659–675 (1986).

  4. 4.

    Short-range order in two eukaryotic genomes: relation to chromosome structure. J. Mol. Biol. 259, 579–588 (1996).

  5. 5.

    , & Yeast nucleosome DNA pattern: deconvolution from genome sequences of S. cerevisiae. J. Biomol. Struct. Dyn. 22, 687–694 (2005).

  6. 6.

    , & Periodical distribution of transcription factor sites in promoter regions and connection with chromatin structure. Proc. Natl. Acad. Sci. USA 96, 2891–2895 (1999).

  7. 7.

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

  8. 8.

    & Nucleosome packaging and nucleosome positioning of genomic DNA. Proc. Natl. Acad. Sci. USA 94, 1183–1188 (1997).

  9. 9.

    , , , & Genome-wide analysis of the relationship between transcriptional regulation by Rpd3p and the histone H3 and H4 amino termini in budding yeast. Mol. Cell. Biol. 24, 8823–8833 (2004).

  10. 10.

    , & Identification and distinct regulation of yeast TATA box-containing genes. Cell 116, 699–709 (2004).

  11. 11.

    & A genome-wide housekeeping role for TFIID and a highly regulated stress-related role for SAGA in Saccharomyces cerevisiae. Mol. Cell 13, 573–585 (2004).

  12. 12.

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

  13. 13.

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

  14. 14.

    et al. Genome-wide map of nucleosome acetylation and methylation in yeast. Cell 122, 517–527 (2005).

  15. 15.

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

  16. 16.

    , , , & Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature 423, 241–254 (2003).

  17. 17.

    & Full and partial genome-wide assembly and disassembly of the yeast transcription machinery in response to heat shock. Genes Dev. 20, 2250–2265 (2006).

  18. 18.

    , & Applicability of the multiple alignment algorithm for detection of weak patterns: periodically distributed DNA pattern as a study case. Comput. Appl. Biosci. 12, 383–389 (1996).

  19. 19.

    et al. Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95, 717–728 (1998).

  20. 20.

    , , & Cluster analysis and display of genome-wide expression patterns. Proc. Natl. Acad. Sci. USA 95, 14863–14868 (1998).

  21. 21.

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

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We thank E.N. Trifonov (University of Haifa), members of the Pugh laboratory and the Center for Gene Regulation for many discussions. This work was supported by US National Institutes of Health grant GM59055 to B.F.P.

Author information


  1. Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio 43210, USA.

    • Ilya P Ioshikhes
  2. Bioinformatics Consulting Center, Huck Institutes for Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.

    • Istvan Albert
  3. Center for Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.

    • Sara J Zanton
    •  & B Franklin Pugh


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I.P.I conducted the computational correlation searches and wrote parts of the paper. I.A. made the nucleosomal calls and developed the associated browser. S.J.Z. performed all relationship studies with public genome-wide data. B.F.P. directed the work, including data analysis, figure assembly, and manuscript writing.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to B Franklin Pugh.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Composite NPS landscape from Fig. 2b in which the DNA sequence was randomized separately in the genic and intergenic region.

  2. 2.

    Supplementary Fig. 2

    Different transcriptional classes of genes have similar NPS magnitudes.

  3. 3.

    Supplementary Fig. 3

    NPS correlation profiles superimposed on ChIP-chip profiles from Yuan et al.

  4. 4.

    Supplementary Fig. 4

    Experimentally mapped nucleosomes superimposed on screen shots from http://nucleosomes.sysbio.bx.psu.edu of NPS profiles.

  5. 5.

    Supplementary Fig. 5

    Number of nucleosome predictions located at 10-bp intervals from the locations determined by Yuan et al.

  6. 6.

    Supplementary Table 3

    Relationship between computationally determined NPS locations and experimentally mapped nucleosome positions.

Excel files

  1. 1.

    Supplementary Table 1

    Relationships between gene clusters and genomic properties available in the public domain.

  2. 2.

    Supplementary Table 2

    Gene-by-gene location of nucleosome positioning sequences.

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