Nucleosome positions predicted through comparative genomics

Abstract

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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Figure 1: Composite NPS landscape of different classes of genes.
Figure 2: Cluster plot of NPS correlation profiles for 6,000 yeast genes.
Figure 3: NPS and positioned-nucleosome landscape at selected genomic regions.
Figure 4: Model depicting the arrangement of NPSs at two classes of promoters.

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Acknowledgements

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.

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Contributions

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.

Corresponding author

Correspondence to B Franklin Pugh.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Composite NPS landscape from Fig. 2b in which the DNA sequence was randomized separately in the genic and intergenic region. (PDF 219 kb)

Supplementary Fig. 2

Different transcriptional classes of genes have similar NPS magnitudes. (PDF 329 kb)

Supplementary Fig. 3

NPS correlation profiles superimposed on ChIP-chip profiles from Yuan et al. (PDF 502 kb)

Supplementary Fig. 4

Experimentally mapped nucleosomes superimposed on screen shots from http://nucleosomes.sysbio.bx.psu.edu of NPS profiles. (PDF 480 kb)

Supplementary Fig. 5

Number of nucleosome predictions located at 10-bp intervals from the locations determined by Yuan et al. (PDF 112 kb)

Supplementary Table 1

Relationships between gene clusters and genomic properties available in the public domain. (XLS 3171 kb)

Supplementary Table 2

Gene-by-gene location of nucleosome positioning sequences. (XLS 3180 kb)

Supplementary Table 3

Relationship between computationally determined NPS locations and experimentally mapped nucleosome positions. (PDF 37 kb)

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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

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