Abstract
We assess the role of intrinsic histone-DNA interactions by mapping nucleosomes assembled in vitro on genomic DNA. Nucleosomes strongly prefer yeast DNA over Escherichia coli DNA, indicating that the yeast genome evolved to favor nucleosome formation. Many yeast promoter and terminator regions intrinsically disfavor nucleosome formation, and nucleosomes assembled in vitro show strong rotational positioning. Nucleosome arrays generated by the ACF assembly factor have fewer nucleosome-free regions, reduced rotational positioning and less translational positioning than obtained by intrinsic histone-DNA interactions. Notably, nucleosomes assembled in vitro have only a limited preference for specific translational positions and do not show the pattern observed in vivo. Our results argue against a genomic code for nucleosome positioning, and they suggest that the nucleosomal pattern in coding regions arises primarily from statistical positioning from a barrier near the promoter that involves some aspect of transcriptional initiation by RNA polymerase II.
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Acknowledgements
We thank I. Albert, Z. Zhang and F. Pugh for analyses and commentary during the early stages of this work, and Y. Lei and H. Shin for help with the heat maps and power spectrum analysis, respectively. This work was supported by grants to J.T.K. (GM 58272), X.S.L. (HG 4069) and K.S. (GM 30186) from the US National Institutes of Health.
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Y.Z. performed all the bioinformatic analyses and contributed to writing of the manuscript; Z.M. prepared the genomic DNAs and the sonicated DNA sample, prepared the micrococcal nuclease–treated samples for DNA sequencing and contributed to the experimental design, data analysis and writing of the manuscript; B.P.R. assembled nucleosomes on genomic DNAs; J.T.K. contributed to experimental design and analysis of the nucleosome samples; G.E. sequenced the DNA samples with contributions from M.S.; X.S.L. contributed to the design and interpretation of the bioinformatic analyses and writing the manuscript; K.S. conceived of the project, contributed to the data analysis and wrote most of the manuscript.
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Zhang, Y., Moqtaderi, Z., Rattner, B. et al. Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo. Nat Struct Mol Biol 16, 847–852 (2009). https://doi.org/10.1038/nsmb.1636
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DOI: https://doi.org/10.1038/nsmb.1636
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