Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays

Peter J. Sabo, Michael S. Kuehn, Robert Thurman, Brett E. Johnson, Ericka M. Johnson, Hua Cao, Man Yu, Elizabeth Rosenzweig, Jeff Goldy, Andrew Haydock, Molly Weaver, Anthony Shafer, Kristin Lee, Fidencio Neri, Richard Humbert, Michael A. Singer, Todd A. Richmond, Michael O. Dorschner, Michael McArthur, Michael HawrylyczRoland D. Green, Patrick A. Navas, William S. Noble, John A. Stamatoyannopoulos

Research output: Contribution to journalArticlepeer-review

253 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)511-518
Number of pages8
JournalNature Methods
Volume3
Issue number7
DOIs
StatePublished - Jul 2006
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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