High-throughput localization of functional elements by quantitative chromatin profiling

Nat Methods. 2004 Dec;1(3):219-25. doi: 10.1038/nmeth721. Epub 2004 Nov 18.


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.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, P.H.S.
  • Validation Study

MeSH terms

  • Algorithms*
  • Cell Line
  • Chromatin / genetics*
  • Chromosome Mapping / methods*
  • Deoxyribonuclease I / genetics*
  • Erythroid Cells / enzymology
  • Genes, Regulator / genetics
  • Genome, Human
  • Humans
  • Polymerase Chain Reaction / methods*
  • Quantitative Trait Loci / genetics*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sequence Alignment / methods
  • Sequence Analysis, DNA / methods*


  • Chromatin
  • Deoxyribonuclease I