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.
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Richmond, T.J. & Davey, C.A. The structure of DNA in the nucleosome core. Nature 423, 145–150 (2003).
Ioshikhes, I., Bolshoy, A., Derenshteyn, K., Borodovsky, M. & Trifonov, E.N. Nucleosome DNA sequence pattern revealed by multiplea alignment of experimentally mapped sequences. J. Mol. Biol. 262, 129–139 (1996).
Satchwell, S.C., Drew, H.R. & Travers, A.A. Sequence periodicities in chicken nucleosome core DNA. J. Mol. Biol. 191, 659–675 (1986).
Widom, J. Short-range order in two eukaryotic genomes: relation to chromosome structure. J. Mol. Biol. 259, 579–588 (1996).
Cohanim, A.B., Kashi, Y. & Trifonov, E.N. Yeast nucleosome DNA pattern: deconvolution from genome sequences of S. cerevisiae. J. Biomol. Struct. Dyn. 22, 687–694 (2005).
Ioshikhes, I., Trifonov, E.N. & Zhang, M.Q. Periodical distribution of transcription factor sites in promoter regions and connection with chromatin structure. Proc. Natl. Acad. Sci. USA 96, 2891–2895 (1999).
Segal, E. et al. A genomic code for nucleosome positioning. Nature 442, 772–778 (2006).
Lowary, P.T. & Widom, J. Nucleosome packaging and nucleosome positioning of genomic DNA. Proc. Natl. Acad. Sci. USA 94, 1183–1188 (1997).
Sabet, N., Volo, S., Yu, C., Madigan, J.P. & Morse, R.H. 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).
Basehoar, A.D., Zanton, S.J. & Pugh, B.F. Identification and distinct regulation of yeast TATA box-containing genes. Cell 116, 699–709 (2004).
Huisinga, K.L. & Pugh, B.F. 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).
Yuan, G.C. et al. Genome-scale identification of nucleosome positions in S. cerevisiae. Science 309, 626–630 (2005).
Zhang, Z. & Dietrich, F.S. Mapping of transcription start sites in Saccharomyces cerevisiae using 5′ SAGE. Nucleic Acids Res. 33, 2838–2851 (2005).
Pokholok, D.K. et al. Genome-wide map of nucleosome acetylation and methylation in yeast. Cell 122, 517–527 (2005).
Cliften, P. et al. Finding functional features in Saccharomyces genomes by phylogenetic footprinting. Science 301, 71–76 (2003).
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).
Zanton, S.J. & Pugh, B.F. Full and partial genome-wide assembly and disassembly of the yeast transcription machinery in response to heat shock. Genes Dev. 20, 2250–2265 (2006).
Bolshoy, A., Ioshikhes, I. & Trifonov, E.N. 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).
Holstege, F.C. et al. Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95, 717–728 (1998).
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).
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).
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.
The authors declare no competing financial interests.
Composite NPS landscape from Fig. 2b in which the DNA sequence was randomized separately in the genic and intergenic region. (PDF 219 kb)
Different transcriptional classes of genes have similar NPS magnitudes. (PDF 329 kb)
NPS correlation profiles superimposed on ChIP-chip profiles from Yuan et al. (PDF 502 kb)
Experimentally mapped nucleosomes superimposed on screen shots from http://nucleosomes.sysbio.bx.psu.edu of NPS profiles. (PDF 480 kb)
Number of nucleosome predictions located at 10-bp intervals from the locations determined by Yuan et al. (PDF 112 kb)
Relationships between gene clusters and genomic properties available in the public domain. (XLS 3171 kb)
Gene-by-gene location of nucleosome positioning sequences. (XLS 3180 kb)
Relationship between computationally determined NPS locations and experimentally mapped nucleosome positions. (PDF 37 kb)
About this article
Cite this article
Ioshikhes, I., Albert, I., Zanton, S. et al. Nucleosome positions predicted through comparative genomics. Nat Genet 38, 1210–1215 (2006). https://doi.org/10.1038/ng1878
Current Genetics (2020)
PLOS Computational Biology (2020)
Soft Computing (2019)
Intracellular nucleosomes constrain a DNA linking number difference of −1.26 that reconciles the Lk paradox
Nature Communications (2018)
International Journal of Molecular Sciences (2018)