High-throughput localization of functional elements by quantitative chromatin profiling

Michael O Dorschner, Michael Hawrylycz, Richard Humbert, James C Wallace, Anthony Shafer, Janelle Kawamoto, Joshua Mack, Robert Hall, Jeff Goldy, Peter J Sabo, Ajay Kohli, Qiliang Li, Michael McArthur, John A Stamatoyannopoulos

Research output: Contribution to journalArticle

91 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)219-25
Number of pages7
JournalNature Methods
Volume1
Issue number3
DOIs
Publication statusPublished - Dec 2004

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

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