Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C)

Nat Genet. 2006 Nov;38(11):1348-54. doi: 10.1038/ng1896. Epub 2006 Oct 8.


The spatial organization of DNA in the cell nucleus is an emerging key contributor to genomic function. We developed 4C technology (chromosome conformation capture (3C)-on-chip), which allows for an unbiased genome-wide search for DNA loci that contact a given locus in the nuclear space. We demonstrate here that active and inactive genes are engaged in many long-range intrachromosomal interactions and can also form interchromosomal contacts. The active beta-globin locus in fetal liver preferentially contacts transcribed, but not necessarily tissue-specific, loci elsewhere on chromosome 7, whereas the inactive locus in fetal brain contacts different transcriptionally silent loci. A housekeeping gene in a gene-dense region on chromosome 8 forms long-range contacts predominantly with other active gene clusters, both in cis and in trans, and many of these intra- and interchromosomal interactions are conserved between the tissues analyzed. Our data demonstrate that chromosomes fold into areas of active chromatin and areas of inactive chromatin and establish 4C technology as a powerful tool to study nuclear architecture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / embryology
  • Cell Nucleus / chemistry*
  • Chromatin / chemistry*
  • Chromatin Assembly and Disassembly*
  • Chromosome Mapping / methods
  • Chromosomes, Mammalian / chemistry*
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation
  • Globins / genetics
  • In Situ Hybridization, Fluorescence / methods
  • Liver / cytology
  • Liver / embryology
  • Mice
  • Models, Biological
  • Nucleic Acid Conformation*
  • Oligonucleotide Array Sequence Analysis / methods*


  • Chromatin
  • DNA-Binding Proteins
  • Rad23a protein, mouse
  • Globins

Associated data

  • GEO/GSE5891