Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays.
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.
Sabo
Peter J
PJ
Department of Genome Sciences, University of Washington, 1705 NE Pacific St., Box 357730, Seattle, Washington 98195, USA.
Kuehn
Michael S
MS
Thurman
Robert
R
Johnson
Brett E
BE
Johnson
Ericka M
EM
Cao
Hua
H
Yu
Man
M
Rosenzweig
Elizabeth
E
Goldy
Jeff
J
Haydock
Andrew
A
Weaver
Molly
M
Shafer
Anthony
A
Lee
Kristin
K
Neri
Fidencio
F
Humbert
Richard
R
Singer
Michael A
MA
Richmond
Todd A
TA
Dorschner
Michael O
MO
McArthur
Michael
M
Hawrylycz
Michael
M
Green
Roland D
RD
Navas
Patrick A
PA
Noble
William S
WS
Stamatoyannopoulos
John A
JA
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
D002843:Chromatin; D003850:Deoxyribonuclease I