title: Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays.
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.
authors.affiliation: Department of Genome Sciences, University of Washington, 1705 NE Pacific St., Box 357730, Seattle, Washington 98195, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sabo
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kuehn
authors.forename: Robert
authors.initials: R
authors.lastname: Thurman
authors.forename: Brett E
authors.initials: BE
authors.lastname: Johnson
authors.forename: Ericka M
authors.initials: EM
authors.lastname: Johnson
authors.forename: Hua
authors.initials: H
authors.lastname: Cao
authors.forename: Man
authors.initials: M
authors.lastname: Yu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rosenzweig
authors.forename: Jeff
authors.initials: J
authors.lastname: Goldy
authors.forename: Andrew
authors.initials: A
authors.lastname: Haydock
authors.forename: Molly
authors.initials: M
authors.lastname: Weaver
authors.forename: Anthony
authors.initials: A
authors.lastname: Shafer
authors.forename: Kristin
authors.initials: K
authors.lastname: Lee
authors.forename: Fidencio
authors.initials: F
authors.lastname: Neri
authors.forename: Richard
authors.initials: R
authors.lastname: Humbert
authors.forename: Michael A
authors.initials: MA
authors.lastname: Singer
authors.forename: Todd A
authors.initials: TA
authors.lastname: Richmond
authors.forename: Michael O
authors.initials: MO
authors.lastname: Dorschner
authors.forename: Michael
authors.initials: M
authors.lastname: McArthur
authors.forename: Michael
authors.initials: M
authors.lastname: Hawrylycz
authors.forename: Roland D
authors.initials: RD
authors.lastname: Green
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Navas
authors.forename: William S
authors.initials: WS
authors.lastname: Noble
authors.forename: John A
authors.initials: JA
authors.lastname: Stamatoyannopoulos
mesh_terms: D002843:Chromatin / Q000737:chemistry; D003850:Deoxyribonuclease I / Q000737:chemistry* / Q000235:genetics; D016678:Genome; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D002843:Chromatin; D003850:Deoxyribonuclease I