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Determinants of nucleosome organization in primary human cells

Nature volume 474, pages 516–520 (2011)Cite this article

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Abstract

Nucleosomes are the basic packaging units of chromatin, modulating accessibility of regulatory proteins to DNA and thus influencing eukaryotic gene regulation. Elaborate chromatin remodelling mechanisms have evolved that govern nucleosome organization at promoters, regulatory elements, and other functional regions in the genome1. Analyses of chromatin landscape have uncovered a variety of mechanisms, including DNA sequence preferences, that can influence nucleosome positions2,3,4. To identify major determinants of nucleosome organization in the human genome, we used deep sequencing to map nucleosome positions in three primary human cell types and in vitro. A majority of the genome showed substantial flexibility of nucleosome positions, whereas a small fraction showed reproducibly positioned nucleosomes. Certain sites that position in vitro can anchor the formation of nucleosomal arrays that have cell type-specific spacing in vivo. Our results unveil an interplay of sequence-based nucleosome preferences and non-nucleosomal factors in determining nucleosome organization within mammalian cells.

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Figure 1: Global parameters of cell-specific nucleosome phasing and positioning in human.
Figure 2: Transcription and chromatin modification-dependent nucleosome spacing.
Figure 3: Sequence signals that drive nucleosome positioning.
Figure 4: Influence of gene regulatory function on nucleosome positioning.

Accession codes

Primary accessions

Sequence Read Archive

Data deposits

All sequence data were submitted to Sequence Read Archive (accession number GSE25133). Sites containing strongly positioned in vitro nucleosomes are available as a supplementary data file.

Change history

  • 23 June 2011

    A figure citation was corrected in the paragraph beginning, 'To explore how regulatory factors interact...".

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Acknowledgements

This work was supported by the Stanford Genetics/Pathology Sequencing Initiative. We thank G. Narlikar for help with in vitro experiments, Life Technologies, especially J. Briggs, for help with generating sequencing data, P. Lacroute for help with sequence alignment, S. Galli for valuable discussions, L. Gracey for critical reading of the manuscript, and members of the Sidow and Fire labs for valuable feedback and discussions. Work in the Fire lab was partially supported by NIGMS (R01GM37706). A.V. was partially supported by an ENCODE subcontract to A.S. (NHGRI U01HG004695). S.M.J. was partially supported by the Stanford Genome Training program (NHGRI T32HG00044).

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Authors and Affiliations

  1. Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, 94305, California, USA

    Anton Valouev, Scott D. Boyd, Cheryl L. Smith, Andrew Z. Fire & Arend Sidow

  2. Department of Microbiology and Molecular Biology, Brigham Young University, 757 WIDB, Provo, 84602-5253, Utah, USA

    Steven M. Johnson

  3. Department of Genetics, Stanford University School of Medicine, Pasteur Drive, Stanford, 94305, California, USA

    Andrew Z. Fire & Arend Sidow

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  1. Anton Valouev
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Contributions

A.V., S.M.J., A.S. and A.Z.F. designed the experiments. S.M.J., A.V., C.L.S. and S.D.B. performed the experiments. A.V. designed and carried out analyses with input from A.S., A.Z.F. and S.M.J.; A.V., A.S. and A.Z.F. wrote the manuscript.

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Correspondence to Andrew Z. Fire or Arend Sidow.

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The authors declare no competing financial interests.

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Valouev, A., Johnson, S., Boyd, S. et al. Determinants of nucleosome organization in primary human cells. Nature 474, 516–520 (2011). https://doi.org/10.1038/nature10002

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