학술논문
Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays.
Document Type
Article
Author
Sabo, Peter J.; Kuehn, Michael S.; Thurman, Robert; Johnson, Brett E.; Johnson, Ericka M.; Hua Cao; Man Yu; 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
Source
Subject
*GENOMES
*HUMAN genome
*DNA microarrays
*CHROMATIN
*GENES
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Language
ISSN
1548-7091
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% (∼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. [ABSTRACT FROM AUTHOR]