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

Sabo, Peter J, Kuehn, Michael S, Thurman, Robert, Johnson, Brett E, Johnson, Ericka M, Cao, Hua, Yu, Man, Rosenzweig, Elizabeth, Goldy, Jeff, Haydock, Andrew, Weaver, Molly, Shafer, Anthony, Lee, Kristin, Neri, Fidencio, Humbert, Richard, Singer, Michael A, Richmond, Todd A, Dorschner, Michael O, McArthur, Michael, Hawrylycz, Michael, Green, Roland D, Navas, Patrick A, Noble, William S and Stamatoyannopoulos, John A (2006) Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays. Nature Methods, 3 (7). pp. 511-8. ISSN 1548-7091

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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.

Item Type: Article
Uncontrolled Keywords: chromatin,deoxyribonuclease i,genome,humans,oligonucleotide array sequence analysis,regulatory sequences, nucleic acid
Faculty \ School: Faculty of Science > The Sainsbury Laboratory
Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User: Pure Connector
Date Deposited: 20 Jan 2014 16:50
Last Modified: 19 Oct 2023 01:14
DOI: 10.1038/nmeth890

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