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
Subscription info for Japanese customers
We have a dedicated website for our Japanese customers. Please go to natureasia.com to subscribe to this journal.
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
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).
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).
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).
Cremer, T. et al. Chromosome territories — a functional nuclear landscape. Curr. Opin. Cell Biol. 18, 307–316 (2006).
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).
Parada, L. & Misteli, T. Chromosome positioning in the interphase nucleus. Trends Cell Biol. 12, 425–432 (2002).
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).
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).
Xu, N., Tsai, C. L. & Lee, J. T. Transient homologous chromosome pairing marks the onset of X inactivation. Science 311, 1149–1152 (2006).
Bacher, C. P. et al. Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation. Nature Cell Biol. 8, 293–299 (2006).
Kurz, A. et al. Active and inactive genes localize preferentially in the periphery of chromosome territories. J. Cell Biol. 135, 1195–1205 (1996).
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).
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).
Brown, J. M. et al. Coregulated human globin genes are frequently in spatial proximity when active. J. Cell Biol. 172, 177–187 (2006).
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).
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).
Chambeyron, S. & Bickmore, W. A. Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. Genes Dev. 18, 1119–1130 (2004).
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).
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).
Chuang, C. H. et al. Long-range directional movement of an interphase chromosome site. Curr. Biol. 16, 825–831 (2006).
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).
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).
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).
Sadoni, N. & Zink, D. Nascent RNA synthesis in the context of chromatin architecture. Chromosome Res. 12, 439–451 (2004).
Osborne, C. S. et al. Active genes dynamically colocalize to shared sites of ongoing transcription. Nature Genet. 36, 1065–1071 (2004).
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).
Chubb, J. R., Trcek, T., Shenoy, S. M. & Singer, R. H. Transcriptional pulsing of a developmental gene. Curr. Biol. 16, 1018–1025 (2006).
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).
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).
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).
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).
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).
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).
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).
Serizawa, S. et al. Negative feedback regulation ensures the one receptor–one olfactory neuron rule in mouse. Science 302, 2088–2094 (2003).
Lomvardas, S. et al. Interchromosomal interactions and olfactory receptor choice. Cell 126, 403–413 (2006).
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).
Morey, C. & Bickmore, W. Sealed with a X. Nature Cell Biol. 8, 207–209 (2006).
LaSalle, J. M. & Lalande, M. Homologous association of oppositely imprinted chromosomal domains. Science 272, 725–728 (1996).
Ling, J. Q. et al. CTCF mediates interchromosomal colocalization between Igf2/H19 and Wsb1/Nf1. Science 312, 269–272 (2006).
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).
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).
Eggan, K. et al. Mice cloned from olfactory sensory neurons. Nature 428, 44–49 (2004).
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).
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
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
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
Published:
Issue Date:
DOI: https://doi.org/10.1038/nature05916