Using formaldehyde-assisted isolation of regulatory elements (FAIRE) to isolate active regulatory DNA

Nat Protoc. 2012 Jan 19;7(2):256-67. doi: 10.1038/nprot.2011.444.


Eviction or destabilization of nucleosomes from chromatin is a hallmark of functional regulatory elements in eukaryotic genomes. Historically identified by nuclease hypersensitivity, these regulatory elements are typically bound by transcription factors or other regulatory proteins. FAIRE (formaldehyde-assisted isolation of regulatory elements) is an alternative approach to identify these genomic regions and has proven successful in a multitude of eukaryotic cell and tissue types. Cells or dissociated tissues are cross-linked briefly with formaldehyde, lysed and sonicated. Sheared chromatin is subjected to phenol/chloroform extraction and the isolated DNA, typically encompassing 1-3% of the human genome, is purified. We provide guidelines for quantitative analysis by PCR, microarrays or next-generation sequencing. Regulatory elements enriched by FAIRE have high concordance with those identified by nuclease hypersensitivity or chromatin immunoprecipitation (ChIP), and the entire procedure can be completed in 3 d. FAIRE has low technical variability, which allows its usage in large-scale studies of chromatin from normal or diseased tissues.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromatin / chemistry
  • Cross-Linking Reagents
  • Formaldehyde
  • Nucleosomes / chemistry
  • Oligonucleotide Array Sequence Analysis / methods
  • Polymerase Chain Reaction / methods
  • Regulatory Elements, Transcriptional*
  • Sequence Analysis, DNA / methods*
  • Software
  • Sonication


  • Chromatin
  • Cross-Linking Reagents
  • Nucleosomes
  • Formaldehyde