High-throughput localization of functional elements by quantitative chromatin profiling

Dorschner, Michael O, Hawrylycz, Michael, Humbert, Richard, Wallace, James C, Shafer, Anthony, Kawamoto, Janelle, Mack, Joshua, Hall, Robert, Goldy, Jeff, Sabo, Peter J, Kohli, Ajay, Li, Qiliang, McArthur, Michael and Stamatoyannopoulos, John A (2004) High-throughput localization of functional elements by quantitative chromatin profiling. Nature Methods, 1 (3). pp. 219-25. ISSN 1548-7091

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Abstract

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 approximately 300 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.

Item Type:	Article
Uncontrolled Keywords:	algorithms,cell line,chromatin,chromosome mapping,deoxyribonuclease i,erythroid cells,genes, regulator,genome, human,humans,polymerase chain reaction,quantitative trait loci,reproducibility of results,sensitivity and specificity,sequence alignment,sequence analysis, dna
Faculty \ School:	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:	06 Jan 2014 14:20
Last Modified:	19 Oct 2023 01:14
URI:	https://ueaeprints.uea.ac.uk/id/eprint/46624
DOI:	10.1038/nmeth721

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