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A genomic code for nucleosome positioning

Abstract

Eukaryotic genomes are packaged into nucleosome particles that occlude the DNA from interacting with most DNA binding proteins. Nucleosomes have higher affinity for particular DNA sequences, reflecting the ability of the sequence to bend sharply, as required by the nucleosome structure. However, it is not known whether these sequence preferences have a significant influence on nucleosome position in vivo, and thus regulate the access of other proteins to DNA. Here we isolated nucleosome-bound sequences at high resolution from yeast and used these sequences in a new computational approach to construct and validate experimentally a nucleosome–DNA interaction model, and to predict the genome-wide organization of nucleosomes. Our results demonstrate that genomes encode an intrinsic nucleosome organization and that this intrinsic organization can explain 50% of the in vivo nucleosome positions. This nucleosome positioning code may facilitate specific chromosome functions including transcription factor binding, transcription initiation, and even remodelling of the nucleosomes themselves.

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Figure 1: Probabilistic nucleosome–DNA interaction model.
Figure 2: Genome-wide prediction of intrinsic nucleosome organization and comparison to literature-reported, experimentally identified 31 nucleosome positions.
Figure 5: Genomes encode unstable nucleosomes at transcriptional start sites.
Figure 3: Higher-order features of intrinsic nucleosome organization and comparison with in vivo occupancy experiments.
Figure 4: Intrinsic nucleosome occupancy varies with genomic location type and is low at functional transcription factor binding sites.

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Acknowledgements

We thank A. Travers for providing the chicken nucleosome core DNA sequences; M. Kubista for providing selected mouse DNA sequences; O. Rando for providing access to their nucleosome data before publication; J. Lieb, E. Nili and P. Jones for sharing their respective unpublished data; Y. Lubling for creating the supplementary website; and H. Chang, N. Friedman, U. Gaul, A. Matouschek, B. Meyer, M. Ptashne, E. Siggia and A. Tanay for useful comments on the manuscript. E.S. was supported by a fellowship from the Center for Studies in Physics and Biology at Rockefeller University and by an NIH grant. J.W. thanks the Center for their hospitality during a sabbatical. J.-P.Z.W. acknowledges support from an NIH grant and J.W. acknowledges support from two NIH grants. E.S. is the incumbent of the Soretta and Henry Shapiro career development chair.

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Correspondence to Eran Segal or Jonathan Widom.

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Supplementary Notes

This file contains the Supplementary Figures 1–40, Supplementary Table 1, Supplementary Methods and Supplementary Notes. Supplementary Methods describe the data sets, molecular biology methods, computational models, and algorithms used. Supplementary Figures include many additional experimental and computational results. Supplementary Notes describe the role of periodicities and phase relationships of key dinucleotide steps, and the properties of our yeast nucleosome collection in comparison to literature-reported nucleosome positions. (PDF 1545 kb)

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Segal, E., Fondufe-Mittendorf, Y., Chen, L. et al. A genomic code for nucleosome positioning. Nature 442, 772–778 (2006). https://doi.org/10.1038/nature04979

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