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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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.).
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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.
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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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DOI: https://doi.org/10.1038/nature11142
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