Global Mapping of Open Chromatin Regulatory Elements by Formaldehyde-Assisted Isolation of Regulatory Elements Followed by Sequencing (FAIRE-seq)

  • Stéphanie Bianco
  • Sébastien Rodrigue
  • Bruce D. Murphy
  • Nicolas GévryEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1334)


Genetic information is organized in a complex structure composed of DNA and proteins together designated chromatin. Chromatin plays a dynamic role in transcriptional processes in that alteration of the interaction between its components results in the deregulation of cellular transcriptional program. Modification of epigenetic marks, variation in the precise positioning of nucleosomes, and consequent mobilization of nucleosomes regulate the access of various transcriptional factors to its underlying DNA template. Nucleosome-depleted regions, also designated open chromatin domains, are associated with active DNA regulatory elements, including promoters, enhancers, silencers, and insulators. Here, we describe the protocol of a rapid and simple technique entitled FAIRE (formaldehyde-assisted isolation of regulatory elements). Combined with high-throughput sequencing (FAIRE-seq), this procedure allows isolation of nucleosome-free regions and their mapping along the genome, thereby providing a global view of cell-specific regulatory elements.

Key words

Chromatin Formaldehyde Regulatory elements Next-generation sequencing Protein–DNA interaction Epigenetics Chromatin accessibility Nucleosome-depleted regions 



We thank Alain Lavigueur and Maïka Jangal for critical comments on the manuscript.


  1. 1.
    Hogan C, Varga-Weisz P (2007) The regulation of ATP-dependent nucleosome remodelling factors. Mutat Res 618(1-2):41–51CrossRefPubMedGoogle Scholar
  2. 2.
    Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21(3):381–395PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Jin J, Cai Y, Li B et al (2005) In and out: histone variant exchange in chromatin. Trends Biochem Sci 30(12):680–687CrossRefPubMedGoogle Scholar
  4. 4.
    Cockerill PN (2011) Structure and function of active chromatin and DNase I hypersensitive sites. FEBS J 278(13):2182–2210CrossRefPubMedGoogle Scholar
  5. 5.
    Rizzo JM, Sinha S (2014) Analyzing the global chromatin structure of keratinocytes by MNase-Seq. Methods Mol Biol 1195:49–59CrossRefPubMedGoogle Scholar
  6. 6.
    Gaulton KJ, Nammo T, Pasquali L et al (2010) A map of open chromatin in human pancreatic islets. Nat Genet 42(3):255–259PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Paul DS, Albers CA, Rendon A et al (2013) Maps of open chromatin highlight cell type-restricted patterns of regulatory sequence variation at hematological trait loci. Genome Res 23(7):1130–1141PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Song L, Zhang Z, Grasfeder LL et al (2011) Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity. Genome Res 21(10):1757–1767PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Waki H, Nakamura M, Yamauchi T et al (2011) Global mapping of cell type-specific open chromatin by FAIRE-seq reveals the regulatory role of the NFI family in adipocyte differentiation. PLoS Genet 7(10), e1002311PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Rodrigue S, Materna AC, Timberlake SC et al (2010) Unlocking short read sequencing for metagenomics. PLoS One 5(7), e11840PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25(14):1754–1760PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Lassmann T, Hayashizaki Y, Daub CO (2011) SAMStat: monitoring biases in next generation sequencing data. Bioinformatics 27(1):130–131PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Zhang Y, Liu T, Meyer CA et al (2008) Model-based analysis of ChIP-Seq (MACS). Genome Biol 9(9):R137PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Boyle AP, Guinney J, Crawford GE et al (2008) F-Seq: a feature density estimator for high-throughput sequence tags. Bioinformatics 24(21):2537–2538PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Thorvaldsdottir H, Robinson JT, Mesirov JP (2013) Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform 14(2):178–192PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Stéphanie Bianco
    • 1
  • Sébastien Rodrigue
    • 1
  • Bruce D. Murphy
    • 2
  • Nicolas Gévry
    • 1
    Email author
  1. 1.Département de Biologie, Faculté des SciencesUniversité de SherbrookeSherbrookeCanada
  2. 2.Centre de Recherche en Reproduction Animale, Faculté de Médecine VétérinaireUniversité de MontréalSaint HyacintheCanada

Personalised recommendations