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:

Chromosome territories, nuclear architecture and gene regulation in mammalian cells

Abstract

The expression of genes is regulated at many levels. Perhaps the area in which least is known is how nuclear organization influences gene expression. Studies of higher-order chromatin arrangements and their dynamic interactions with other nuclear components have been boosted by recent technical advances. The emerging view is that chromosomes are compartmentalized into discrete territories. The location of a gene within a chromosome territory seems to influence its access to the machinery responsible for specific nuclear functions, such as transcription and splicing. This view is consistent with a topological model for gene regulation.

Key Points

  • Chromosomes occupy discrete territories in the cell nucleus and contain distinct chromosome-arm and chromosome-band domains.

  • Chromosome territories (CTs) with different gene densities occupy distinct nuclear positions.

  • Gene-poor, mid-to-late-replicating chromatin is enriched in nuclear compartments that are located at the nuclear periphery and at the perinucleolar region.

  • A compartment for gene-dense, early-replicating chromatin is separated from the compartments for mid-to-late-replicating chromatin.

  • Chromatin domains with a DNA content of 1 Mb can be detected in nuclei during interphase and in non-cycling cells.

  • The interchromatin compartment (IC) contains various types of non-chromatin domains with factors for transcription, splicing, DNA replication and repair.

  • The CT–IC model predicts that a specific topological relationship between the IC and chromatin domains is essential for gene regulation.

  • The transcriptional status of genes correlates with gene positioning in CTs.

  • A dynamic repositioning of genes with respect to centromeric heterochromatin has a role in gene silencing and activation.

  • Various computer models of CTs and nuclear architecture make different predictions that can be validated by experimental tests.

  • Comprehensive understanding of gene regulation requires much more detailed knowledge of gene expression in the context of nuclear architecture and organization.

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: Model of functional nuclear architecture.
Figure 2: Chromosome territories in the chicken.
Figure 3: Features of human chromosome territories.
Figure 4: Gene-rich and gene-poor chromosome territories.
Figure 5: Early- and mid-to-late-replicating chromatin domains.
Figure 6: The interchromatin compartment.
Figure 7: The multiloop subcompartment model.

Similar content being viewed by others

References

  1. El-Osta, A. & Wolffe, A. P. DNA methylation and histone deacetylation in the control of gene expression: basic biochemistry to human development and disease. Gene Expression 9, 63– 75 (2000).

    Article  CAS  PubMed  Google Scholar 

  2. Bell, A. C. & Felsenfeld, G. Stopped at the border: boundaries and insulators. Curr. Opin. Genet. Dev. 9, 191–198 (1999).

    Article  CAS  PubMed  Google Scholar 

  3. Blobel, G. Gene gating: a hypothesis. Proc. Natl Acad. Sci. USA 82, 8527–8530 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Manuelidis, L. A view of interphase chromosomes. Science 250, 1533–1540 (1990). An excellent attempt to integrate a multitude of experimental findings in the framework of a functional higher-order chromatin architecture. This paper is still a 'must read'.

    Article  CAS  PubMed  Google Scholar 

  5. Cremer, T. et al. Role of chromosome territories in the functional compartmentalization of the cell nucleus. Cold Spring Harb. Symp. Quant. Biol. 58, 777–792 (1993).

    Article  CAS  PubMed  Google Scholar 

  6. Spector, D. L. Nuclear organization and gene expression. Exp. Cell Res. 229, 189–197 (1996).

    Article  CAS  PubMed  Google Scholar 

  7. Berezney, R. & Wei, X. The new paradigm: integrating genomic function and nuclear architecture. J. Cell. Biochem. 31, S238–S242 (1998).

    Article  Google Scholar 

  8. Lamond, A. I. & Earnshaw, W. C. Structure and function in the nucleus. Science 280, 547– 553 (1998).

    Article  CAS  PubMed  Google Scholar 

  9. Park, P. C. & De Boni, U. Dynamics of structure–function relationships in interphase nuclei. Life Sci. 64, 1703–1718 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. Marshall, W. F. & Sedat, J. W. Nuclear architecture . Results Probl. Cell Differ. 25, 283– 301 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Chevret, E., Volpi, E. V. & Sheer, D. Mini review: form and function in the human interphase chromosome. Cytogenet. Cell Genet. 90, 13 –21 (2000).

    Article  CAS  PubMed  Google Scholar 

  12. Cremer, T. et al. Chromosome territories, interchromatin domain compartment and nuclear matrix. An integrated view of the functional nuclear architecture . Crit. Rev. Eukaryotic Gene Expression 12, 179–212 (2000).

    Google Scholar 

  13. Gonzalez-Melendi, P. et al. The nucleus: a highly organized but dynamic structure. J. Microsc. 198, 199–207 (2000).

    Article  CAS  PubMed  Google Scholar 

  14. Leitch, A. R. Higher levels of organization in the interphase nucleus of cycling and differentiated cells. Microbiol. Mol. Biol. Rev. 64, 138 –152 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Carmo-Fonseca, M., Mendes-Soares, L. & Campos, I. To be or not to be in the nucleolus. Nature Cell Biol. 2, E107–E112 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. Stoffler, D., Fahrenkrog, B. & Aebi, U. The nuclear pore complex: from molecular architecture to functional dynamics. Curr. Opin. Cell Biol. 11, 391–401 (1999).

    Article  CAS  PubMed  Google Scholar 

  17. van der Ploeg, M. Cytochemical nucleic acid research during the twentieth century. Eur. J. Histochem. 44, 7–42 (2000).A thorough historical account of in situ hybridization from its beginnings to present-day technologies.

    CAS  PubMed  Google Scholar 

  18. Stack, S. M., Brown, D. B. & Dewey, W. C. Visualization of interphase chromosomes. J. Cell Sci. 26, 281–299 (1977).

    Article  CAS  PubMed  Google Scholar 

  19. Zorn, C., Cremer, C., Cremer, T. & Zimmer, J. Unscheduled DNA synthesis after partial UV irradiation of the cell nucleus. Distribution in interphase and metaphase. Exp. Cell Res. 124, 111–119 (1979).

    Article  CAS  PubMed  Google Scholar 

  20. Dietzel, S. et al. Separate and variably shaped chromosome arm domains are disclosed by chromosome arm painting in human cell nuclei. Chromosome Res. 6, 25–33 (1998 ).

    Article  CAS  PubMed  Google Scholar 

  21. 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  PubMed  Google Scholar 

  22. Dietzel, S. et al. The 3D positioning of ANT2 and ANT3 genes within female X chromosome territories correlates with gene activity. Exp. Cell Res. 252, 363–375 (1999).

    Article  CAS  PubMed  Google Scholar 

  23. 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). Activation of specific genes from the major histocompatibility locus correlates with an expansion of the gene-harbouring chromatin loops from the surface of chromosome-6 territories.

    Article  CAS  PubMed  Google Scholar 

  24. Park, P. C. & De Boni, U. A specific conformation of the territory of chromosome 17 locates ERBB-2 sequences to a DNase-hypersensitive domain at the nuclear periphery. Chromosoma 107, 87–95 (1998).

    Article  CAS  PubMed  Google Scholar 

  25. Ferreira, J., Paolella, G., Ramos, C. & Lamond, A. I. Spatial organization of large-scale chromatin domains in the nucleus: a magnified view of single chromosome territories. J. Cell Biol. 139, 1597–1610 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zink, D., Bornfleth, H., Visser, A., Cremer, C. & Cremer, T. Organization of early and late replicating DNA in human chromosome territories. Exp. Cell Res. 247, 176–188 (1999).

    Article  CAS  PubMed  Google Scholar 

  27. Verschure, P. J., van Der Kraan, I., Manders, E. M. & van Driel, R. Spatial relationship between transcription sites and chromosome territories . J. Cell Biol. 147, 13– 24 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Visser, A. E., Jaunin, F., Fakan, S. & Aten, J. A. High resolution analysis of interphase chromosome domains. J. Cell Sci. 113, 2585–2593 (2000).

    Article  CAS  PubMed  Google Scholar 

  29. Solovei, I. et al. Topology of double minutes (dmins) and homogeneously staining regions (HSRs) in nuclei of human neuroblastoma cell lines. Genes Chromosom. Cancer 29, 297–308 (2000).

    Article  CAS  PubMed  Google Scholar 

  30. Zink, D. et al. Structure and dynamics of human interphase chromosome territories in vivo. Hum. Genet. 102, 241– 251 (1998).First demonstration of chromosome territories in the living-cell nucleus.

    Article  CAS  PubMed  Google Scholar 

  31. Manders, E. M., Kimura, H. & Cook, P. R. Direct imaging of DNA in living cells reveals the dynamics of chromosome formation. J. Cell Biol. 144, 813–821 (1999).This in vivo study relates the gross structure of a chromosome territory to that of a prophase chromosome.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bornfleth, H., Edelmann, P., Zink, D., Cremer, T. & Cremer, C. Quantitative motion analysis of subchromosomal foci in living cells using four-dimensional microscopy. Biophys. J. 77, 2871–2886 ( 1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. De Boni, U. The interphase nucleus as a dynamic structure. Int. Rev. Cytol. 150, 149–171 ( 1994).

    Article  CAS  PubMed  Google Scholar 

  34. Borden, J. & Manuelidis, L. Movement of the X chromosome in epilepsy. Science 242, 1687– 1691 (1988).

    Article  CAS  PubMed  Google Scholar 

  35. Csink, A. K. & Henikoff, S. Large-scale chromosomal movements during interphase progression in Drosophila. J. Cell Biol. 143, 13–22 ( 1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nagele, R., Freeman, T., McMorrow, L. & Lee, H. Y. Precise spatial positioning of chromosomes during prometaphase: evidence for chromosomal order. Science 270, 1831– 1835 (1995).

    Article  CAS  PubMed  Google Scholar 

  37. Allison, D. C. & Nestor, A. L. Evidence for a relatively random array of human chromosomes on the mitotic ring. J. Cell Biol. 145, 1–14 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chandley, A. C., Speed, R. M. & Leitch, A. R. Different distributions of homologous chromosomes in adult human Sertoli cells and in lymphocytes signify nuclear differentiation . J. Cell Sci. 109, 773– 776 (1996).

    Article  CAS  PubMed  Google Scholar 

  39. Comings, D. E. Arrangement of chromatin in the nucleus. Hum. Genet. 53, 131–143 (1980).

    Article  CAS  PubMed  Google Scholar 

  40. Sun, H. B., Shen, J. & Yokota, H. Size-dependent positioning of human chromosomes in interphase nuclei. Biophys. J. 79, 184– 190 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Boyle, S. et al. The spatial organization of human chromosomes within the nuclei of normal and emerin-mutant cells. Hum. Mol. Genet. 10, 211–219 (2001).

    Article  CAS  PubMed  Google Scholar 

  42. Croft, J. A. et al. Differences in the localization and morphology of chromosomes in the human nucleus. J. Cell Biol. 145, 1119–1131 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Henikoff, S. Nuclear organization and gene expression: homologous pairing and long- range interactions. Curr. Opin. Cell Biol. 9, 388–395 (1997).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  45. O'Brien, S. J. et al. The promise of comparative genomics in mammals. Science 286, 458–462, 479 –481 (1999). Pubmed

    Article  CAS  PubMed  Google Scholar 

  46. Craig, J. M. & Bickmore, W. A. The distribution of CpG islands in mammalian chromosomes. Nature Genet. 7, 376–382 (1994); erratum 7, 551 (1994). Pubmed

    Article  CAS  PubMed  Google Scholar 

  47. Dietzel, S. et al. Evidence against a looped structure of the inactive human X-chromosome territory. Exp. Cell Res. 240, 187–196 (1998).

    Article  CAS  PubMed  Google Scholar 

  48. Sadoni, N. et al. Nuclear organization of mammalian genomes. Polar chromosome territories build up functionally distinct higher order compartments. J. Cell Biol. 146, 1211–1226 (1999).Describes evidence that chromosome territories contribute to gene-rich and gene-poor higher-order chromatin compartments.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kennedy, B. K., Barbie, D. A., Classon, M., Dyson, N. & Harlow, E. Nuclear organization of DNA replication in primary mammalian cells. Genes Dev. 14, 2855–2868 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Chan, J. K., Park, P. C. & De Boni, U. Association of DNase sensitive chromatin domains with the nuclear periphery in 3T3 cells in vitro. Biochem. Cell Biol. 78, 67–78 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  51. Leonhardt, H. et al. Dynamics of DNA replication factories in living cells. J. Cell Biol. 149, 271–280 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ma, H. et al. Spatial and temporal dynamics of DNA replication sites in mammalian cells. J. Cell Biol. 143, 1415– 1425 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Sparvoli, E., Levi, M. & Rossi, E. Replicon clusters may form structurally stable complexes of chromatin and chromosomes. J. Cell Sci. 107, 3097– 3103 (1994).

    Article  CAS  PubMed  Google Scholar 

  54. Jackson, D. A. & Pombo, A. Replicon clusters are stable units of chromosome structure: evidence that nuclear organization contributes to the efficient activation and propagation of S phase in human cells. J. Cell Biol. 140, 1285– 1295 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Shankar Narayan, K., Steele, W. J., Smetana, K. & Busch, H. Ultrastructural aspects of the ribonucleoprotein network in nuclei of walker tumor and rat liver. Exp. Cell Res. 46, 65–77 (1967).

    Article  Google Scholar 

  56. Kanda, T., Sullivan, K. F. & Wahl, G. M. Histone–GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells. Curr. Biol. 8, 377–385 ( 1998).

    Article  CAS  PubMed  Google Scholar 

  57. Matera, A. G. Nuclear bodies: multifaceted subdomains of the interchromatin space. Trends Cell Biol. 9, 302–309 (1999).

    Article  CAS  PubMed  Google Scholar 

  58. Brasch, K. & Ochs, R. L. Nuclear bodies (NBs): a newly 'rediscovered' organelle. Exp. Cell Res. 202, 211– 223 (1992).

    Article  CAS  PubMed  Google Scholar 

  59. Misteli, T. Cell biology of transcription and pre-mRNA splicing: nuclear architecture meets nuclear function. J. Cell Sci. 113, 1841–1849 (2000).

    Article  CAS  PubMed  Google Scholar 

  60. Misteli, T. Protein dynamics: implications for nuclear architecture and gene expression . Science 291, 843–847 (2001).A summary of the evidence that movement of proteins in the nucleus to their site of action occurs by simple diffusion.

    Article  CAS  PubMed  Google Scholar 

  61. Singer, R. H. & Green, M. R. Compartmentalization of eukaryotic gene expression: causes and effects. Cell 91, 291–294 (1997).

    Article  CAS  PubMed  Google Scholar 

  62. Politz, J. C., Tuft, R. A., Pederson, T. & Singer, R. H. Movement of nuclear poly(A) RNA throughout the interchromatin space in living cells. Curr. Biol. 9, 285– 291 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Kruhlak, M. J. et al. Reduced mobility of the alternate splicing factor (ASF) through the nucleoplasm and steady state speckle compartments. J. Cell Biol. 150, 41–51 ( 2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Wachsmuth, M., Waldeck, W. & Langowski, J. Anomalous diffusion of fluorescent probes inside living cell nuclei investigated by spatially-resolved fluorescence correlation spectroscopy . J. Mol. Biol. 298, 677– 689 (2000).

    Article  CAS  PubMed  Google Scholar 

  65. Lukacs, G. L. et al. Size-dependent DNA mobility in cytoplasm and nucleus. J. Biol. Chem. 275, 1625–1629 (2000).

    Article  CAS  PubMed  Google Scholar 

  66. Zirbel, R. M., Mathieu, U. R., Kurz, A., Cremer, T. & Lichter, P. Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries. Chromosome Res. 1, 93–106 ( 1993).

    Article  CAS  PubMed  Google Scholar 

  67. 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  PubMed  PubMed Central  Google Scholar 

  68. Cmarko, D. et al. Ultrastructural analysis of transcription and splicing in the cell nucleus after bromo-UTP microinjection. Mol. Biol. Cell 10, 211–223 ( 1999).Electron-microscopic evidence that nascent RNA is synthesized at chromatin-domain surfaces.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Fakan, S. Perichromatin fibrils are in situ forms of nascent trancripts. Trends Cell Biol. 4, 86–90 (1994).

    Article  CAS  PubMed  Google Scholar 

  70. Nickerson, J. A. Experimental observations of a nuclear matrix. J. Cell Sci. 114, 463–474 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Cremer, T., Dietzel, S., Eils, R., Lichter, P. & Cremer, C. in Kew Chromosome Conference IV (ed. Benett, M. D.) 63–81 (Royal Botanic Gardens, Kew, 1995).

    Google Scholar 

  72. Münkel, C. et al. Compartmentalization of interphase chromosomes observed in simulation and experiment. J. Mol. Biol. 285, 1053–1065 (1999). Chromosome territories are simulated as a flexible fibre, assuming an arrangement of 120-kb loops into rosette-like subcompartments. The resulting model structure agrees well with experimental observations.

    Article  PubMed  Google Scholar 

  73. Pederson, T. Half a century of 'the nuclear matrix'. Mol. Biol. Cell 11, 799–805 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Cook, P. R. The organization of replication and transcription. Science 284, 1790–1795 (1999).

    Article  CAS  PubMed  Google Scholar 

  75. Misteli, T., Caceres, J. F. & Spector, D. L. The dynamics of a pre-mRNA splicing factor in living cells. Nature 387, 523– 527 (1997).

    Article  CAS  PubMed  Google Scholar 

  76. Smith, K. P., Moen, P. T., Wydner, K. L., Coleman, J. R. & Lawrence, J. B. Processing of endogenous pre-mRNAs in association with SC-35 domains is gene specific. J. Cell Biol. 144, 617–629 ( 1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Dernburg, A. F. et al. Perturbation of nuclear architecture by long-distance chromosome interactions. Cell 85, 745– 759 (1996).This study indicates that in Drosophila , the brown gene is silenced by specific contact with centromeric heterochromatin.

    Article  CAS  PubMed  Google Scholar 

  78. Brown, K. E. et al. Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin. Cell 91, 845–854 (1997).Evidence that repressed genes in mouse B lymphocytes are selectively recruited into centromeric heterochromatin domains.

    Article  CAS  PubMed  Google Scholar 

  79. Brown, K. E., Baxter, J., Graf, D., Merkenschlager, M. & Fisher, A. G. Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division. Mol. Cell 3, 207–217 (1999).

    Article  CAS  PubMed  Google Scholar 

  80. Schübeler, D. et al. Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human β-globin locus. Genes Dev. 14, 940– 950 (2000).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Francastel, C., Walters, M. C., Groudine, M. & Martin, D. I. A functional enhancer suppresses silencing of a transgene and prevents its localization close to centrometric heterochromatin. Cell 99, 259–269 (1999).

    Article  CAS  PubMed  Google Scholar 

  82. Lundgren, M. et al. Transcription factor dosage affects changes in higher order chromatin structure associated with activation of a heterochromatic gene. Cell 103, 733–743 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  83. Gerasimova, T. I., Byrd, K. & Corces, V. G. A chromatin insulator determines the nuclear localization of DNA. Mol. Cell 6, 1025– 1035 (2000).

    Article  CAS  PubMed  Google Scholar 

  84. Robinett, C. C. et al. In vivo localization of DNA sequences and visualization of large-scale chromatin organization using lac operator/repressor recognition . J. Cell Biol. 135, 1685– 1700 (1996).

    Article  CAS  PubMed  Google Scholar 

  85. Tsukamoto, T. et al. Visualization of gene activity in living cells. Nature Cell Biol. 2, 871–878 (2000).The first experimental design simultaneously to visualize a transgene and to monitor its expression in a living cell.

    Article  CAS  PubMed  Google Scholar 

  86. Tumbar, T. & Belmont, A. Interphase movements of a DNA chromosome region modulated by VP16 transcriptional activator. Nature Cell Biol. 3, 134–139 ( 2001).An approach for the in vivo localization of DNA sequences first described in reference 84 is used here to examine changes in intranuclear chromosome positioning that are induced by a transcriptional activator.

    Article  CAS  PubMed  Google Scholar 

  87. Alberts, B. et al. Molecular Biology of the Cell (Garland, Inc., New York & London, 1994).

    Google Scholar 

  88. Belmont, A. S. & Bruce, K. Visualization of G1 chromosomes: a folded, twisted, supercoiled chromonema model of interphase chromatid structure. J. Cell Biol. 127, 287–302 (1994).

    Article  CAS  PubMed  Google Scholar 

  89. Kreth, G., Münkel, C., Langowski, J., Cremer, T. & Cremer, C. Chromatin structure and chromosome aberrations: modeling of damage induced by isotropic and localized irradiation . Mutat. Res. 404, 77–88 (1998).

    Article  CAS  PubMed  Google Scholar 

  90. Sachs, R. K., van den Engh, G., Trask, B., Yokota, H. & Hearst, J. E. A random-walk/giant-loop model for interphase chromosomes. Proc. Natl Acad. Sci. USA 92, 2710–2714 (1995). First quantitative modelling of gene distances in distinct chromosome territories.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kreth, G., Edelmann, P., Münkel, C., Langowski, J. & Cremer, C. in Chromosome Structure and Function (eds Sobti, R. C., Obe, G. & Athwal, R. S.) (in the press).

  92. Ostashevsky, J. Higher-order structure of interphase chromosomes and radiation-induced chromosomal exchange aberrations. Int. J. Radiat. Biol. 76, 1179–1187 (2000).

    Article  CAS  PubMed  Google Scholar 

  93. Sachs, R. K., Hlatky, L. R. & Trask, B. J. Radiation-produced chromosome aberrations: colourful clues. Trends Genet. 16, 143– 146 (2000).

    Article  CAS  PubMed  Google Scholar 

  94. Monneron, A. & Bernhard, W. Fine structural organization of the interphase nucleus in some mammalian cells. J. Ultrastruct. Res. 27, 266–288 ( 1969).

    Article  CAS  PubMed  Google Scholar 

  95. Woodcock, C. L. & Horowitz, R. A. Chromatin organization reviewed. Trends Cell Biol. 5, 272–277 (1995).

    Article  CAS  PubMed  Google Scholar 

  96. Puvion, E. & Puvion-Dutilleul, F. Ultrastructure of the nucleus in relation to transcription and splicing: roles of perichromatin fibrils and interchromatin granules. Exp. Cell Res. 229, 217–225 (1996).

    Article  CAS  PubMed  Google Scholar 

  97. Cremer, T. et al. Rabl's model of the interphase chromosome arrangement tested in Chinese hamster cells by premature chromosome condensation and laser-UV-microbeam experiments. Hum. Genet. 60, 46– 56 (1982).

    Article  CAS  PubMed  Google Scholar 

  98. Berns, M. W., Wright, W. H. & Wiegand Steubing, R. Laser microbeam as a tool in cell biology . Int. Rev. Cytol. 129, 1– 44 (1991).

    Article  CAS  PubMed  Google Scholar 

  99. Phair, R. D. & Misteli, T. High mobility of proteins in the mammalian cell nucleus. Nature 404, 604– 609 (2000).

    Article  CAS  PubMed  Google Scholar 

  100. Agard, D. A. & Sedat, J. W. Three-dimensional architecture of a polytene nucleus. Nature 302, 676– 681 (1983).First analysis of the three-dimensional architecture and arrangement of chromosomes in a polytene nucleus on the basis of light optical serial sectioning and deconvolution.

    Article  CAS  PubMed  Google Scholar 

  101. Pawley, J. B. (ed.) Handbook of Biological Confocal Microscopy (Plenum, New York, 1995).

    Book  Google Scholar 

  102. Hänninen, P. E., Hell, S. W., Salo, J., Soini, E. & Cremer, C. Two-photon excitation 4Pi confocal microscope: enhanced axial resolution microscope for biological research. Appl. Phys. Lett. 66, 1698–1700 ( 1995).

    Article  Google Scholar 

  103. Klar, T. A., Jakobs, S., Dyba, M., Egner, A. & Hell, S. W. Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission. Proc. Natl Acad. Sci. USA 97, 8206–8210 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Marshall, W. F. et al. Interphase chromosomes undergo constrained diffusional motion in living cells. Curr. Biol. 7, 930– 939 (1997).

    Article  CAS  PubMed  Google Scholar 

  105. Bornfleth, H., Sätzler, K., Eils, R. & Cremer, C. High-precision distance measurements and volume-conserving segmentation of objects near and below the resolution limit in three-dimensional confocal fluorescence microscopy. J. Microsc. 189, 118–136 (1998).

    Article  Google Scholar 

  106. Damelin, M. & Silver, P. Mapping interactions between nuclear transport factors in living cells reveals pathways through nuclear pore complex . Mol. Cell 5, 133–140 (2000).

    Article  CAS  PubMed  Google Scholar 

  107. Politz, J. C., Browne, E. S., Wolf, D. E. & Pederson, T. Intranuclear diffusion and hybridization state of oligonucleotides measured by fluorescence correlation spectroscopy in living cells. Proc. Natl Acad. Sci. USA 95, 6043–6048 (1998).Using in vivo fluorescence correlation spectroscopy, the authors show that nuclear poly(A) RNA moves by a diffusion-like process.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Schönle, A., Glatz, M. & Hell, S. W. Four-dimensional multiphoton microscopy with time-correlated single-photon counting. Appl. Optics 39, 6306–6311 (2000).

    Article  Google Scholar 

  109. Dirks, R. W., Hattinger, C. M., Molenaar, C. & Snaar, S. P. Synthesis, processing, and transport of RNA within the three-dimensional context of the cell nucleus. Crit. Rev. Eukaryote Gene Expression 9, 191–201 (1999).

    Article  CAS  Google Scholar 

  110. Nakamura, H., Morita, T. & Sato, C. Structural organizations of replicon domains during DNA synthetic phase in the mammalian nucleus. Exp. Cell Res. 165, 291–297 (1986).

    Article  CAS  PubMed  Google Scholar 

  111. Aten, J. A., Stap, J., Hoebe, R. & Bakker, P. J. Application and detection of IdUrd and CldUrd as two independent cell-cycle markers. Methods Cell Biol. 41, 317–326 (1994).

    Article  CAS  PubMed  Google Scholar 

  112. Chalfie, M., Tu, Y., Euskirchen, G., Ward, W. W. & Prasher, D. C. Green fluorescent protein as a marker for gene expression . Science 263, 802–805 (1994).

    Article  CAS  PubMed  Google Scholar 

  113. Heikal, A. A., Hess, S. T., Baird, G. S., Tsien, R. Y. & Webb, W. W. Molecular spectroscopy and dynamics of intrinsically fluorescent proteins: coral red (dsRed) and yellow (Citrine) . Proc. Natl Acad. Sci. USA 97, 11996– 12001 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Ostashevsky, J. A polymer model for the structural organization of chromatin loops and minibands in interphase chromosomes. Mol. Biol. Cell 9, 3031–3040 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Schermelleh, L., Solovei, I., Zink, D. & Cremer, T. Two-color fluorescence labeling of early and mid-to-late replicating chromatin in living cells. Chromosome Res. 9, 77–80 (2001).

    Article  CAS  PubMed  Google Scholar 

  116. Ma, H., Siegel, A. J. & Berezney, R. Association of chromosome territories with the nuclear matrix. Disruption of human chromosome territories correlates with the release of a subset of nuclear matrix proteins. J. Cell Biol. 146, 531–542 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Deutsche Forschungsgemein-schaft, the BMBF (German Human Genome Project) and the German–Israeli Foundation. A first version of the CT–IC model was developed with P. Lichter and others in 1993. We are indebted to our present and past co-workers for helping us to shape the views presented here. We thank S. Fakan, T. Misteli, T. Pederson, R. Driel, L. Zech and several unnamed referees for their helpful comments.

Author information

Authors and Affiliations

Authors

Supplementary information

Related links

Related links

DATABASE LINKS

Prader–Willi syndrome

Angelman syndrome

ANT2

ANT3

Glossary

EPIGENETICS

Any heritable influence (in the progeny of cells or of individuals) on gene activity, unaccompanied by a change in DNA sequence.

CHROMOSOME PAINTING

Visualization of individual, whole chromosomes by fluorescence in situ hybridization (FISH).

CENTROMERIC HETEROCHROMATIN

Comprises the genetically inert, constitutive heterochromatin of the centromere and is built up from tandem repetitive DNA sequences.

EPIFLUORESCENCE MICROSCOPY

The entire cell is illuminated and fluorescence is recorded through the same objective from an entire focal plane.

ABBE LIMIT

Theoretical limit of light-microscopic resolution defined in 1873 by Ernst Abbe. This limit holds for conventional light microscopy but can be overcome by new laser microscopic approaches (Box 1).

SPECKLES

Irregularly shaped regions that contain splicing factors. At the electron-microscopic level they correspond to interchromatin granule clusters (IGCs), which function in the storage and supply of components of the pre-mRNA splicing machinery, and perichromatin fibrils located in the vicinity of IGCs.

CAJAL BODIES

(also known as coiled bodies). Nuclear organelles of unknown function named in honour of Ramón y Cajal. Cajal bodies are possibly sites of assembly or modification of the transcription machinery of the nucleus.

PML BODIES

Contain wild-type promyelocytic leukaemia (PML) protein and other proteins. Their function remains elusive, but might be related to transcription control.

CHROMATIN FIBRES

These 30-nm fibres are produced by the compaction of 10-nm nucleosome fibres. Nucleosome fibres are visible under the electron microscope after treatments that unfold higher-order chromatin packaging into a 'beads-on-a-string' 10-nm diameter form.

MICRODISSECTION PROBES

DNA probes established from microdissected chromosomal subregions. The probes are useful for the labelling of chromosome arms and bands.

CONFOCAL LASER SCANNING MICROSCOPES

(CLSM). A three-dimensional cell is illuminated and the fluorescence is recorded point by point.

SC-35 DOMAINS

The essential non-snRNP (small nuclear ribonucleoprotein particles) splicing factor SC-35 shows a speckled distribution in the nucleus that co-localizes with snRNPs in speckles.

LOOP BASE SPRINGS

In the multiloop subcompartment model of chromosome territory architecture, stiff springs were assumed to exist at the loop bases for a simulation of chromosome territory anchor proteins.

CHROMOSOME TERRITORY ANCHOR PROTEINS

Proteins that are essential for the maintenance of chromosome territories.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cremer, T., Cremer, C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2, 292–301 (2001). https://doi.org/10.1038/35066075

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35066075

This article is cited by

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