Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Nuclear organization of the genome and the potential for gene regulation

Abstract

Much work has been published on the cis-regulatory elements that affect gene function locally, as well as on the biochemistry of the transcription factors and chromatin- and histone-modifying complexes that influence gene expression. However, surprisingly little information is available about how these components are organized within the three-dimensional space of the nucleus. Technological advances are now helping to identify the spatial relationships and interactions of genes and regulatory elements in the nucleus and are revealing an unexpectedly extensive network of communication within and between chromosomes. A crucial unresolved issue is the extent to which this organization affects gene function, rather than just reflecting it.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Events of nuclear reorganization during X-chromosome inactivation.
Figure 2: Colocalization of genes in the nucleus for expression or coregulation.
Figure 3: Cis and trans interactions of the H enhancer and olfactory-receptor genes.

Similar content being viewed by others

References

  1. Wurtele, H. & Chartrand, P. Genome-wide scanning of HoxB1-associated loci in mouse ES cells using an open-ended Chromosome Conformation Capture methodology. Chromosome Res. 14, 477–495 (2006).

    Article  Google Scholar 

  2. Zhao, Z. et al. Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions. Nature Genet. 38, 1341–1347 (2006).

    Article  CAS  Google Scholar 

  3. Simonis, M. et al. Nuclear organization of active and inactive chromatin domains uncovered by chromosome conformation capture-on-chip (4C). Nature Genet. 38, 1348–1354 (2006).

    Article  CAS  Google Scholar 

  4. Cremer, T. et al. Chromosome territories — a functional nuclear landscape. Curr. Opin. Cell Biol. 18, 307–316 (2006).

    Article  CAS  Google Scholar 

  5. Bolzer, A. et al. Three-dimensional maps of all chromosomes in human male fibroblast nuclei and prometaphase rosettes. PLoS Biol. [online] 3, e157 (2005) (10.1371/journal.pbio.0030157).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Parada, L. & Misteli, T. Chromosome positioning in the interphase nucleus. Trends Cell Biol. 12, 425–432 (2002).

    Article  CAS  Google Scholar 

  7. Bickmore, W. A. & Teague, P. Influences of chromosome size, gene density and nuclear position on the frequency of constitutional translocations in the human population. Chromosome Res. 10, 707–715 (2002).

    Article  CAS  Google Scholar 

  8. Parada, L. A., McQueen, P. G. & Misteli, T. Tissue-specific spatial organization of genomes. Genome Biol. [online] 5, R44 (2004) (doi: 0.1186/gb-2004-5-7-r44).

    Article  Google Scholar 

  9. Xu, N., Tsai, C. L. & Lee, J. T. Transient homologous chromosome pairing marks the onset of X inactivation. Science 311, 1149–1152 (2006).

    Article  ADS  CAS  Google Scholar 

  10. Bacher, C. P. et al. Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation. Nature Cell Biol. 8, 293–299 (2006).

    Article  CAS  Google Scholar 

  11. Kurz, A. et al. Active and inactive genes localize preferentially in the periphery of chromosome territories. J. Cell Biol. 135, 1195–1205 (1996).

    Article  CAS  Google Scholar 

  12. Mahy, N. L., Perry, P. E., Gilchrist, S., Baldock, R. A. & Bickmore, W. A. Spatial organization of active and inactive genes and noncoding DNA within chromosome territories. J. Cell Biol. 157, 579–589 (2002).

    Article  CAS  Google Scholar 

  13. Mahy, N. L., Perry, P. E. & Bickmore, W. A. Gene density and transcription influence the localization of chromatin outside of chromosome territories detectable by FISH. J. Cell Biol. 159, 753–763 (2002).

    Article  CAS  Google Scholar 

  14. Brown, J. M. et al. Coregulated human globin genes are frequently in spatial proximity when active. J. Cell Biol. 172, 177–187 (2006).

    Article  CAS  Google Scholar 

  15. Volpi, E. V. et al. Large-scale chromatin organization of the major histocompatibility complex and other regions of human chromosome 6 and its response to interferon in interphase nuclei. J. Cell Sci. 113, 1565–1576 (2000).

    CAS  PubMed  Google Scholar 

  16. Williams, R. R., Broad, S., Sheer, D. & Ragoussis, J. Subchromosomal positioning of the epidermal differentiation complex (EDC) in keratinocyte and lymphoblast interphase nuclei. Exp. Cell Res. 272, 163–175 (2002).

    Article  CAS  Google Scholar 

  17. Chambeyron, S. & Bickmore, W. A. Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes Dev. 18, 1119–1130 (2004).

    Article  CAS  Google Scholar 

  18. Morey, C., Da Silva, N. R., Perry, P. & Bickmore, W. A. Nuclear reorganisation and chromatin decondensation are conserved, but distinct, mechanisms linked to Hox gene activation. Development 134, 909–919 (2007).

    Article  CAS  Google Scholar 

  19. Branco, M. R. & Pombo, A. Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations. PLoS Biol. [online] 4, e138 (2006) (doi: 10.1371/journal.pbio.0040138).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chuang, C. H. et al. Long-range directional movement of an interphase chromosome site. Curr. Biol. 16, 825–831 (2006).

    Article  CAS  Google Scholar 

  21. Chubb, J. R., Boyle, S., Perry, P. & Bickmore, W. A. Chromatin motion is constrained by association with nuclear compartments in human cells. Curr. Biol. 12, 439–445 (2002).

    Article  CAS  Google Scholar 

  22. Chaumeil, J., Le Baccon, P., Wutz, A. & Heard, E. A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. Genes Dev. 20, 2223–2237 (2006).

    Article  CAS  Google Scholar 

  23. Abranches, R., Beven, A. F., Aragon-Alcaide, L. & Shaw, P. J. Transcription sites are not correlated with chromosome territories in wheat nuclei. J. Cell Biol. 143, 5–12 (1998).

    Article  CAS  Google Scholar 

  24. Sadoni, N. & Zink, D. Nascent RNA synthesis in the context of chromatin architecture. Chromosome Res. 12, 439–451 (2004).

    Article  CAS  Google Scholar 

  25. Osborne, C. S. et al. Active genes dynamically colocalize to shared sites of ongoing transcription. Nature Genet. 36, 1065–1071 (2004).

    Article  CAS  Google Scholar 

  26. Ragoczy, T., Bender, M. A., Telling, A., Byron, R. & Groudine, M. The locus control region is required for association of the murine beta-globin locus with engaged transcription factories during erythroid maturation. Genes Dev. 20, 1447–1457 (2006).

    Article  CAS  Google Scholar 

  27. Chubb, J. R., Trcek, T., Shenoy, S. M. & Singer, R. H. Transcriptional pulsing of a developmental gene. Curr. Biol. 16, 1018–1025 (2006).

    Article  CAS  Google Scholar 

  28. Iborra, F. J., Pombo, A., Jackson, D. A. & Cook, P. R. Active RNA polymerases are localized within discrete transcription 'factories' in human nuclei. J. Cell Sci. 109, 1427–1436 (1996).

    CAS  PubMed  Google Scholar 

  29. Moen, P. T. Jr et al. Repositioning of muscle-specific genes relative to the periphery of SC-35 domains during skeletal myogenesis. Mol. Biol. Cell 15, 197–206 (2004).

    Article  CAS  Google Scholar 

  30. Shopland, L. S., Johnson, C. V., Byron, M., McNeil, J. & Lawrence, J. B. Clustering of multiple specific genes and gene-rich R-bands around SC-35 domains: evidence for local euchromatic neighborhoods. J. Cell Biol. 162, 981–990 (2003).

    Article  CAS  Google Scholar 

  31. Xie, S. Q., Martin, S., Guillot, P. V., Bentley, D. L. & Pombo, A. Splicing speckles are not reservoirs of RNA polymerase II, but contain an inactive form, phosphorylated on serine2 residues of the C-terminal domain. Mol. Biol. Cell 17, 1723–1733 (2006).

    Article  CAS  Google Scholar 

  32. Johnson, C. et al. Tracking COL1A1 RNA in osteogenesis imperfecta. Splice-defective transcripts initiate transport from the gene but are retained within the SC35 domain. J. Cell Biol. 150, 417–432 (2000).

    Article  CAS  Google Scholar 

  33. Molenaar, C., Abdulle, A., Gena, A., Tanke, H. J. & Dirks, R. W. Poly(A)+ RNAs roam the cell nucleus and pass through speckle domains in transcriptionally active and inactive cells. J. Cell Biol. 165, 191–202 (2004).

    Article  CAS  Google Scholar 

  34. Shopland, L. S. et al. Folding and organization of a contiguous chromosome region according to the gene distribution pattern in primary genomic sequence. J. Cell Biol. 174, 27–38 (2006).

    Article  CAS  Google Scholar 

  35. Serizawa, S. et al. Negative feedback regulation ensures the one receptor–one olfactory neuron rule in mouse. Science 302, 2088–2094 (2003).

    Article  ADS  CAS  Google Scholar 

  36. Lomvardas, S. et al. Interchromosomal interactions and olfactory receptor choice. Cell 126, 403–413 (2006).

    Article  CAS  Google Scholar 

  37. Spilianakis, C. G., Lalioti, M. D., Town, T., Lee, G. R. & Flavell, R. A. Interchromosomal associations between alternatively expressed loci. Nature 435, 637–645 (2005).

    Article  ADS  CAS  Google Scholar 

  38. Morey, C. & Bickmore, W. Sealed with a X. Nature Cell Biol. 8, 207–209 (2006).

    Article  CAS  Google Scholar 

  39. LaSalle, J. M. & Lalande, M. Homologous association of oppositely imprinted chromosomal domains. Science 272, 725–728 (1996).

    Article  ADS  CAS  Google Scholar 

  40. Ling, J. Q. et al. CTCF mediates interchromosomal colocalization between Igf2/H19 and Wsb1/Nf1. Science 312, 269–272 (2006).

    Article  ADS  CAS  Google Scholar 

  41. Sproul, D., Gilbert, N. & Bickmore, W. A. The role of chromatin structure in regulating the expression of clustered genes. Nature Rev. Genet. 6, 775–781 (2005).

    Article  CAS  Google Scholar 

  42. Chakalova, L., Debrand, E., Mitchell, J. A., Osborne, C. S. & Fraser, P. Replication and transcription: shaping the landscape of the genome. Nature Rev. Genet. 6, 669–677 (2005).

    Article  CAS  Google Scholar 

  43. Eggan, K. et al. Mice cloned from olfactory sensory neurons. Nature 428, 44–49 (2004).

    Article  ADS  CAS  Google Scholar 

  44. Li, J., Ishii, T., Feinstein, P. & Mombaerts, P. Odorant receptor gene choice is reset by nuclear transfer from mouse olfactory sensory neurons. Nature 428, 393–399 (2004).

    Article  ADS  CAS  Google Scholar 

Download references

Acknowledgements

P.F. is a Senior Fellow of the Medical Research Council UK and receives support from the Biotechnology and Biological Sciences Research Council, UK. W.B. is a Centennial fellow of the James S. McDonnell Foundation, is supported by the Medical Research Council UK and acknowledges the contribution of the EU FP6 Epigenome Network of Excellence.

Author information

Authors and Affiliations

Authors

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Reprints and permissions information is available at http://npg.nature.com/reprintsandpermissions. Correspondence should be addressed to W.B. (w.bickmore@hgu.mrc.ac.uk) or P.F. (peter.fraser@bbsrc.ac.uk).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fraser, P., Bickmore, W. Nuclear organization of the genome and the potential for gene regulation. Nature 447, 413–417 (2007). https://doi.org/10.1038/nature05916

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05916

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing