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

Nature Genetics volume 38, pages 1348–1354 (2006)Cite this article

Abstract

The spatial organization of DNA in the cell nucleus is an emerging key contributor to genomic function1,2,3,4,5,6,7,8,9,10,11,12. 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 β-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.

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Acknowledgements

We thank F. Grosveld for support and discussion and S. van Baal, M. Branco, A. Pombo, P. Verrijzer, J. Hou, B. Eussen, A. de Klein, T. de Vries Lentsch, D. Noordermeer and R.-J. Palstra for assistance. This work was supported by grants from the Dutch Scientific Organization (NWO) (912-04-082) and the Netherlands Genomics Initiative (050-71-324) to W.L.

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Authors and Affiliations

  1. Department of Cell Biology and Genetics, Erasmus Medical Centre, PO Box 2040, Rotterdam, 3000 CA, The Netherlands
    Marieke Simonis, Petra Klous, Erik Splinter & Wouter de Laat
  2. Department of Biochemistry, Erasmus Medical Centre, PO Box 2040, Rotterdam, 3000 CA, The Netherlands
    Yuri Moshkin
  3. Department of Clinical Genetics, Erasmus Medical Centre, PO Box 2040, Rotterdam, 3000 CA, The Netherlands
    Rob Willemsen
  4. Division of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands
    Elzo de Wit & Bas van Steensel

Authors

  1. Marieke Simonis
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  2. Petra Klous
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  3. Erik Splinter
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  4. Yuri Moshkin
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  5. Rob Willemsen
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  6. Elzo de Wit
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  7. Bas van Steensel
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  8. Wouter de Laat
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Contributions

M.S. set up, performed and analyzed 4C experiments and wrote the paper; P.K. performed cryo-FISH experiments; E.S. helped set up 4C; Y.M. helped with statistical analysis; R.W. prepared cryosections; E.d.W. and B.v.S. provided probe sequences and helped with statistical analysis and W.d.L. designed experiments and wrote the paper.

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Correspondence toWouter de Laat.

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Simonis, M., Klous, P., Splinter, E. et al. Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture–on-chip (4C).Nat Genet 38, 1348–1354 (2006). https://doi.org/10.1038/ng1896

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