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Article
Nature Methods - 1, 219 - 225 (2004)
Published online: 18 November 2004; | doi:10.1038/nmeth721

High-throughput localization of functional elements by quantitative chromatin profiling

Michael O Dorschner1, Michael Hawrylycz1, Richard Humbert1, James C Wallace1, Anthony Shafer1, Janelle Kawamoto1, Joshua Mack1, Robert Hall1, Jeff Goldy1, Peter J Sabo1, Ajay Kohli2, Qiliang Li2, Michael McArthur1 & John A Stamatoyannopoulos1

1  Department of Molecular Biology, Regulome, 2211 Elliott Avenue, Suite 600, Seattle, Washington 98121, USA.

2  Division of Medical Genetics, University of Washington, K–253 Health Sciences Building, Box 357720, 1705 NE Pacific Street, Seattle, Washington 98105, USA.

Correspondence should be addressed to John A Stamatoyannopoulos jstam@regulome.com

Identification of functional, noncoding elements that regulate transcription in the context of complex genomes is a major goal of modern biology. Localization of functionality to specific sequences is a requirement for genetic and computational studies. Here, we describe a generic approach, quantitative chromatin profiling, that uses quantitative analysis of in vivo chromatin structure over entire gene loci to rapidly and precisely localize cis-regulatory sequences and other functional modalities encoded by DNase I hypersensitive sites. To demonstrate the accuracy of this approach, we analyzed approx300 kilobases of human genome sequence from diverse gene loci and cleanly delineated functional elements corresponding to a spectrum of classical cis-regulatory activities including enhancers, promoters, locus control regions and insulators as well as novel elements. Systematic, high-throughput identification of functional elements coinciding with DNase I hypersensitive sites will substantially expand our knowledge of transcriptional regulation and should simplify the search for noncoding genetic variation with phenotypic consequences.

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Nature Methods
ISSN: 1548-7091
EISSN: 1548-7105
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