title: High-throughput localization of functional elements by quantitative chromatin profiling.
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.
authors.affiliation: Department of Molecular Biology, Regulome, 2211 Elliott Avenue, Suite 600, Seattle, Washington 98121, USA.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Dorschner
authors.forename: Michael
authors.initials: M
authors.lastname: Hawrylycz
authors.forename: Richard
authors.initials: R
authors.lastname: Humbert
authors.forename: James C
authors.initials: JC
authors.lastname: Wallace
authors.forename: Anthony
authors.initials: A
authors.lastname: Shafer
authors.forename: Janelle
authors.initials: J
authors.lastname: Kawamoto
authors.forename: Joshua
authors.initials: J
authors.lastname: Mack
authors.forename: Robert
authors.initials: R
authors.lastname: Hall
authors.forename: Jeff
authors.initials: J
authors.lastname: Goldy
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sabo
authors.forename: Ajay
authors.initials: A
authors.lastname: Kohli
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: McArthur
authors.forename: John A
authors.initials: JA
authors.lastname: Stamatoyannopoulos
mesh_terms: D000465:Algorithms; D002460:Cell Line; D002843:Chromatin / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D003850:Deoxyribonuclease I / Q000235:genetics*; D041905:Erythroid Cells / Q000201:enzymology; D005809:Genes, Regulator / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D016133:Polymerase Chain Reaction / Q000379:methods*; D040641:Quantitative Trait Loci / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D002843:Chromatin; D003850:Deoxyribonuclease I