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Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome

Nature volume 446, pages 572–576 (2007)Cite this article

Abstract

The nucleosome is the fundamental building block of eukaryotic chromosomes. Access to genetic information encoded in chromosomes is dependent on the position of nucleosomes along the DNA. Alternative locations just a few nucleotides apart can have profound effects on gene expression1. Yet the nucleosomal context in which chromosomal and gene regulatory elements reside remains ill-defined on a genomic scale. Here we sequence the DNA of 322,000 individual Saccharomyces cerevisiae nucleosomes, containing the histone variant H2A.Z, to provide a comprehensive map of H2A.Z nucleosomes in functionally important regions. With a median 4-base-pair resolution, we identify new and established signatures of nucleosome positioning. A single predominant rotational setting and multiple translational settings are evident. Chromosomal elements, ranging from telomeres to centromeres and transcriptional units, are found to possess characteristic nucleosomal architecture that may be important for their function. Promoter regulatory elements, including transcription factor binding sites and transcriptional start sites, show topological relationships with nucleosomes, such that transcription factor binding sites tend to be rotationally exposed on the nucleosome surface near its border. Transcriptional start sites tended to reside about one helical turn inside the nucleosome border. These findings reveal an intimate relationship between chromatin architecture and the underlying DNA sequence it regulates.

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Figure 1: Distribution of H2A.Z nucleosomal DNA at an arbitrary region of the yeast genome.
Figure 2: Rotational and translational settings of H2A.Z nucleosomes.
Figure 3: Distribution of H2A.Z nucleosomes in and around chromosomal elements.
Figure 4: Distribution of transcriptional regulatory elements along the nucleosome surface.

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Acknowledgements

We thank R. Albert for computational support, and S. Tan, J. Reese, D. Gilmour, and Y. Wang for many helpful discussions. This work was supported by a grant from NIH.

Author Contributions I.A. developed computational approaches to derive nucleosome maps from the read locations and developed the associated browser; T.N.M. prepared and purified the nucleosomes; L.P.T. constructed libraries and sequenced nucleosomal DNA; J.Q. mapped sequencing reads to the yeast genome; S.J.Z. produced Supplementary Tables 2 and 3; S.C.S. managed and directed the DNA sequencing phase, and analysed the sequencing data; and B.F.P. directed the project, analysed the processed data, and wrote the paper.

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Authors and Affiliations

  1. Center for Comparative Genomics and Bioinformatics,,

    Istvan Albert, Travis N. Mavrich, Lynn P. Tomsho, Ji Qi, Sara J. Zanton, Stephan C. Schuster & B. Franklin Pugh

  2. Department of Biochemistry and Molecular Biology, Center for Gene Regulation, The Pennsylvania State University, University Park, Pennsylvania 16802, USA,

    Travis N. Mavrich, Sara J. Zanton & B. Franklin Pugh

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  1. Istvan Albert
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Correspondence to B. Franklin Pugh.

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Supplementary information

Supplementary Information

This file contains Supplementary Methods, Supplementary Figures S1-S9 with Legends, Supplementary Table 2 and additional references. (PDF 3883 kb)

Supplementary Table 1

This file contains Supplementary Table 1. The Supplementary Table 1 contains the chromosomal coordinates of the top 46,809 translational settings (fine-grain positions) of the top 17,758 H2A.Z –containing coarse-grain nucleosomes. (XLS 12769 kb)

Supplementary Table 2

This file contains Supplementary Table 3. The Supplementary Table 3 contains additional and more detailed relationships between “very fuzzy” or “very wide” nucleosomes and published genomic information, than presented in Supplementary Table S2. (XLS 12730 kb)

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Albert, I., Mavrich, T., Tomsho, L. et al. Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome. Nature 446, 572–576 (2007). https://doi.org/10.1038/nature05632

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