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A map of nucleosome positions in yeast at base-pair resolution

Abstract

The exact positions of nucleosomes along genomic DNA can influence many aspects of chromosome function. However, existing methods for mapping nucleosomes do not provide the necessary single-base-pair accuracy to determine these positions. Here we develop and apply a new approach for direct mapping of nucleosome centres on the basis of chemical modification of engineered histones. The resulting map locates nucleosome positions genome-wide in unprecedented detail and accuracy. It shows new aspects of the in vivo nucleosome organization that are linked to transcription factor binding, RNA polymerase pausing and the higher-order structure of the chromatin fibre.

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Figure 1: Mapping nucleosome centres by site-specific chemical cleavage.
Figure 2: Raw data, defined nucleosomes and pairwise comparison of nucleosome maps.
Figure 3: Nucleosome sequence preferences.
Figure 4: Genome-wide features of nucleosome positions.
Figure 5: Nucleosome spacing and higher-order chromatin structures.
Figure 6: High-resolution nucleosome centre positions relative to genomic features.

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Accession codes

Primary accessions

Gene Expression Omnibus

Data deposits

Sequence data are deposited in National Center for Biotechnology Information Gene Expression Omnibus database under accession number GSE36063.

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Acknowledgements

We dedicate this paper to J.W., who guided this project. We thank R. Holmgren, A. Matouschek, B. Meyer, R. Phillips, E. Segal and O. Uhlenbeck for comments and discussions. We are grateful to Northwestern University’s Genomic Core for all sequencing completed for this project. The work was supported by National Institutes of Health grants T32GM00806 (to K.B.), R01GM058617 (to J.W.), R01GM075313 (to J.-P.W.) and U54CA143869 (to J.W.).

Author information

Authors and Affiliations

Authors

Contributions

K.B. did all the experimental work. L.X. and J.-P.W. developed the algorithm and performed the analyses. K.B., J.-P.W. and J.W. wrote the paper. J.W. directed the project.

Corresponding author

Correspondence to Ji-Ping Wang.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Methods, Supplementary References, Supplementary Figure legends and Supplementary Figures 1-12, Supplementary Table titles 1-3 and Supplementary Table 1 (see separate files for Supplementary Tables 2-3). (PDF 5030 kb)

Supplementary Table 2

This file contains a list of nucleosomes in the unique map with NCP score and NCP score/noise ratio. Tab delimited text file. The names of the four columns are: chromosome ID, position, NCP score and NCP score/noise ratio. This file was replaced online on 21 March 2013. (TXT 2638 kb)

Supplementary Table 3

This file contains a list of nucleosomes in the redundant map with NCP score and NCP score/noise ratio. Tab delimited text file. The names of the four columns are: chromosome ID, position, NCP score and NCP score/noise ratio. This file was replaced online on 21 March 2013. (TXT 13465 kb)

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Brogaard, K., Xi, L., Wang, JP. et al. A map of nucleosome positions in yeast at base-pair resolution. Nature 486, 496–501 (2012). https://doi.org/10.1038/nature11142

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