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

262 Citations (Scopus)

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% ( approximately 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
Pages (from-to)511-8
Number of pages8
JournalNature Methods
Volume3
Issue number7
DOIs
Publication statusPublished - Jul 2006

Keywords

  • Chromatin
  • Deoxyribonuclease I
  • Genome
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Regulatory Sequences, Nucleic Acid

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