Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays (original) (raw)

Nature Methods volume 3, pages 511–518 (2006)Cite this article

Abstract

Localized accessibility of critical DNA sequences to the regulatory machinery is a key requirement for regulation of human genes. Here we describe a high-resolution, genome-scale approach for quantifying chromatin accessibility by measuring DNase I sensitivity as a continuous function of genome position using tiling DNA microarrays (DNase-array). We demonstrate this approach across 1% (∼30 Mb) of the human genome, wherein we localized 2,690 classical DNase I hypersensitive sites with high sensitivity and specificity, and also mapped larger-scale patterns of chromatin architecture. DNase I hypersensitive sites exhibit marked aggregation around transcriptional start sites (TSSs), though the majority mark nonpromoter functional elements. We also developed a computational approach for visualizing higher-order features of chromatin structure. This revealed that human chromatin organization is dominated by large (100–500 kb) 'superclusters' of DNase I hypersensitive sites, which encompass both gene-rich and gene-poor regions. DNase-array is a powerful and straightforward approach for systematic exposition of the _cis_-regulatory architecture of complex genomes.

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Acknowledgements

This work was supported by grants from the US National Institute of General Medical Sciences and the National Human Genome Research Institute to J.A.S. and W.S.N.

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Author notes

  1. Peter J Sabo and Michael S Kuehn: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genome Sciences, University of Washington, 1705 NE Pacific St., Box 357730, Seattle, 98195, Washington, USA
    Peter J Sabo, Michael S Kuehn, Robert Thurman, Jeff Goldy, Andrew Haydock, Molly Weaver, Anthony Shafer, Kristin Lee, Fidencio Neri, Richard Humbert, Michael O Dorschner, William S Noble & John A Stamatoyannopoulos
  2. Division of Medical Genetics, Department of Medicine, University of Washington, 1705 NE Pacific St., Box 357730, Seattle, 98195, Washington, USA
    Michael S Kuehn, Robert Thurman, Brett E Johnson, Ericka M Johnson, Hua Cao, Man Yu, Elizabeth Rosenzweig & Patrick A Navas
  3. Nimblegen Systems, Inc., 1 Science Court, Madison, 53711, Wisconsin, USA
    Michael A Singer, Todd A Richmond & Roland D Green
  4. Department of Microbiology, John Innes Centre, Norwich Research Park, Colney, Norwich, NR4 7UH, UK
    Michael McArthur
  5. Allen Institute for Brain Sciences, 551 N. 34th Street, Seattle, 98103, Washington, USA
    Michael Hawrylycz

Authors

  1. Peter J Sabo
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  2. Michael S Kuehn
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  3. Robert Thurman
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  4. Brett E Johnson
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  5. Ericka M Johnson
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  6. Hua Cao
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  7. Man Yu
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  8. Elizabeth Rosenzweig
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  9. Jeff Goldy
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  10. Andrew Haydock
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  11. Molly Weaver
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  12. Anthony Shafer
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  13. Kristin Lee
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  14. Fidencio Neri
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  15. Richard Humbert
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  16. Michael A Singer
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  17. Todd A Richmond
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  18. Michael O Dorschner
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  19. Michael McArthur
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  20. Michael Hawrylycz
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  21. Roland D Green
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  22. Patrick A Navas
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  23. William S Noble
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  24. John A Stamatoyannopoulos
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Corresponding author

Correspondence toJohn A Stamatoyannopoulos.

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Competing interests

R.D.G. is an employee of NimbleGen Systems, a manufacturer of microarrays, which potentially stands to benefit from the results published in this article.

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Sabo, P., Kuehn, M., Thurman, R. et al. Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays.Nat Methods 3, 511–518 (2006). https://doi.org/10.1038/nmeth890

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