Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions

Nat Genet. 2006 Nov;38(11):1341-7. doi: 10.1038/ng1891. Epub 2006 Oct 8.


Accumulating evidence converges on the possibility that chromosomes interact with each other to regulate transcription in trans. To systematically explore the epigenetic dimension of such interactions, we devised a strategy termed circular chromosome conformation capture (4C). This approach involves a circularization step that enables high-throughput screening of physical interactions between chromosomes without a preconceived idea of the interacting partners. Here we identify 114 unique sequences from all autosomes, several of which interact primarily with the maternally inherited H19 imprinting control region. Imprinted domains were strongly overrepresented in the library of 4C sequences, further highlighting the epigenetic nature of these interactions. Moreover, we found that the direct interaction between differentially methylated regions was linked to epigenetic regulation of transcription in trans. Finally, the patterns of interactions specific to the maternal H19 imprinting control region underwent reprogramming during in vitro maturation of embryonic stem cells. These observations shed new light on development, cancer epigenetics and the evolution of imprinting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Binding Sites
  • CCCTC-Binding Factor
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Chromosomes / chemistry*
  • Cloning, Molecular / methods*
  • DNA-Binding Proteins / metabolism
  • Embryonic Stem Cells
  • Epigenesis, Genetic / physiology*
  • Gene Expression Regulation / genetics*
  • Genomic Imprinting / physiology
  • Liver / metabolism
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • Nucleic Acid Conformation
  • Oligonucleotide Array Sequence Analysis / methods
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics
  • Repressor Proteins / metabolism
  • Trans-Activators


  • CCCTC-Binding Factor
  • Chromatin
  • Ctcf protein, mouse
  • DNA-Binding Proteins
  • H19 long non-coding RNA
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Repressor Proteins
  • Trans-Activators