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- Title
Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays.
- Authors
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; Stamatoyannopoulos, John A
- 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.
- Publication
Nature methods, 2006, Vol 3, Issue 7, p511
- ISSN
1548-7091
- Publication type
Journal Article
- DOI
10.1038/nmeth890