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Article
Nature Methods - 3, 503 - 509 (2006)
Published online: 21 June 2006; | doi:10.1038/nmeth888

DNase-chip: a high-resolution method to identify DNase I hypersensitive sites using tiled microarrays

Gregory E Crawford1, 3, Sean Davis1, Peter C Scacheri1, Gabriel Renaud1, Mohamad J Halawi1, Michael R Erdos1, Roland Green2, Paul S Meltzer1, Tyra G Wolfsberg1 & Francis S Collins1

1  National Human Genome Research Institute, National Institutes of Health, Building 31, Room 4B09, Bethesda, Maryland 20892, USA.

2  NimbleGen Systems, Incorporated, 1 Science Court, Madison, Wisconsin 53711, USA.

3  Present address: Institute for Genome Sciences & Policy, and Department of Pediatrics, 101 Science Drive, CIEMAS Building, Duke University, Box 3382, Durham, North Carolina 27708, USA.

Correspondence should be addressed to Francis S Collins francisc@exchange.nih.gov

Mapping DNase I hypersensitive sites is an accurate method of identifying the location of gene regulatory elements, including promoters, enhancers, silencers and locus control regions. Although Southern blots are the traditional method of identifying DNase I hypersensitive sites, the conventional manual method is not readily scalable to studying large chromosomal regions, much less the entire genome. Here we describe DNase-chip, an approach that can rapidly identify DNase I hypersensitive sites for any region of interest, or potentially for the entire genome, by using tiled microarrays. We used DNase-chip to identify DNase I hypersensitive sites accurately from a representative 1% of the human genome in both primary and immortalized cell types. We found that although most DNase I hypersensitive sites were present in both cell types studied, some of them were cell-type specific. This method can be applied globally or in a targeted fashion to any tissue from any species with a sequenced genome.

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CD4+ T cells and GM06990 cells (Gentra)
Centrisep columns (Princeton Separations)
DNase I (Roche)
ENCODE array (NimbleGen)
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InCert low-melt gel agarose plugs (BioWhittaker)
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Nature Methods
ISSN: 1548-7091
EISSN: 1548-7105
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