Detecting Long-Range Chromatin Interactions Using the Chromosome Conformation Capture Sequencing (4C-seq) Method

  • Nele GheldofEmail author
  • Marion Leleu
  • Daan Noordermeer
  • Jacques Rougemont
  • Alexandre Reymond
Part of the Methods in Molecular Biology book series (MIMB, volume 786)


Eukaryotic transcription is tightly regulated by transcriptional regulatory elements, even though these elements may be located far away from their target genes. It is now widely recognized that these regulatory elements can be brought in close proximity through the formation of chromatin loops, and that these loops are crucial for transcriptional regulation of their target genes. The chromosome conformation capture (3C) technique presents a snapshot of long-range interactions, by fixing physically interacting elements with formaldehyde, digestion of the DNA, and ligation to obtain a library of unique ligation products. Recently, several large-scale modifications to the 3C technique have been presented. Here, we describe chromosome conformation capture sequencing (4C-seq), a high-throughput version of the 3C technique that combines the 3C-on-chip (4C) protocol with next-generation Illumina sequencing. The method is presented for use in mammalian cell lines, but can be adapted to use in mammalian tissues and any other eukaryotic genome.

Key words

Chromosome conformation capture Looping interactions Interactome Regulatory elements 



We are grateful for the help from Keith Harshman, Jérôme Thomas, Floriane Consales, and Emmanuel Beaudoing from the Lausanne Genomic Technologies Facility (GTF). This work was supported by the Marie Heim-Vögtlin fellowship to N.G.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Nele Gheldof
    • 1
    Email author
  • Marion Leleu
    • 2
  • Daan Noordermeer
    • 3
  • Jacques Rougemont
    • 4
  • Alexandre Reymond
    • 1
  1. 1.Center for Integrative GenomicsUniversity of Lausanne, Le Génopode, Quartier UNIL-SorgeLausanneSwitzerland
  2. 2.School of Life Sciences and Bioinformatics and Biostatistics Core FacilitySwiss Institute of Bioinformatics, Ecole Polytechnique Fédérale (EPFL)LausanneSwitzerland
  3. 3.School of Life SciencesEcole Polytechnique Fédérale (EPFL)LausanneSwitzerland
  4. 4.Bioinformatics and Biostatistics Core FacilitySwiss Institute of Bioinformatics, Ecole Polytechnique Fédérale (EPFL)LausanneSwitzerland

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