Cell Cycle: Chromosomal Organization


In interphase nuclei chromosomes are organized as distinct nuclear structures, called chromosome territories (CTs). If CTs and chromosomal subregions are organized in a cell type‐specific or species‐specific manner and if these structures show specific positional changes during the cell cycle then there may be a functionally significant relationship between higher‐order chromatin arrangements and nuclear functions, for example cell cycle‐ and cell type‐specific differences in gene expression.

Keywords: chromosome topology; interphase movement of chromatin; cell cycle; nuclear architecture; chromosome subregions

Figure 1.

Replication pattern of chromatin from a neuroblastoma cell line after double‐pulse labeling during early and mid‐S phase with nucleotides conjugated with different fluorochromes. (a) Light optical section through the nucleus fixed after double‐pulse labeling. The nucleus shows the typical distribution pattern of early‐replicating chromatin expanding in the nuclear interior and of mid‐replicating chromatin concentrated at the nuclear periphery and around nucleoli. (b) Light optical section through a double‐labeled nucleus fixed after three postlabeling cell cycles. The majority of nuclear chromatin remains unlabeled; the labeled chromatin shows polarized chromosome territories with typical early‐ and mid‐replication patterns. (c) The same nucleus as shown in (b) after DNA counterstaining. (d) Metaphase spread prepared from double‐labeled cells demonstrating distinct replication banding pattern of chromosomes. Scale bar for (a)–(c) is 5 μm.

Figure 2.

Distribution of territories from some large and small chromosomes after 3DFISH in nuclei of two cell types. The territories of small chromosomes are painted with a probe set specific for chromosomes 17–20; the territories of the large chromosomes are painted with a probe set specific for chromosomes 1–5. (Image courtesy of Alessandro Brero.) (a) 3D reconstruction (surface rendering, Amira TGS software) of chromosome territories combined with a mid‐plane optical section of the counterstained nucleus (shown in gray) from a human fibroblast. All territories of the small chromosomes are clustered in the nuclear interior, while the territories of the large chromosomes show a peripheral positioning. (b) 3D reconstructions (surface rendering, Amira TGS software) of large and small chromosome territories in two nuclei of human lymphocytes. Territories of the larger chromosomes show a peripheral position compared with the chromosome territory position of the smaller chromosomes. Note, however, the peripheral position of a fraction of painted chromosome territories (marked by an arrow) that probably represent the territory of chromosome 18 (compare Cremer et al., ). Scale bars are 5 μm.

Figure 3.

Representative 3D reconstructions (surface rendering, Amira TGS software) of chromosome territories after painting of chromatin homologous to human chromosome 18 and human chromosome 19 in lymphoblastoid nuclei from different primate species. The chromosome territories are shown together with a partial reconstruction of the DNA‐counterstained nuclear border. (a) Human lymphoblastoid cell. Both territories of chromosome 19 are clustered in the nuclear interior without touching the nuclear border, and the territories of chromosome 18 show a peripheral localization. (b) Common marmoset (Callithrix jacchus) lymphoblastoid cell. In this species, chromosomes homologous to human chromosomes 18 and 19 are entirely conserved except for a segment of chromosome 18 that is translocated to the 8p human homolog. The intranuclear positioning of chromatin homologous to human chromosomes 18 and 19 reveals the same spatial distribution as observed in humans. (c) White‐handed gibbon (Hylobates lar) lymphoblastoid cell. Compared with humans, this species shows a high degree of chromosome reshuffling. The human chromosome 18 homologous segment is associated with the 1p32→q22 human homologous segment while the human chromosome19 homolog is fragmented into four parts, which contribute to three different gibbon chromosomes. Irrespective of these major chromosome rearrangements, human chromosome 18 homologous chromatin is located in proximity to the nuclear envelope, whereas human chromosome 19 homologous material is centrally located, occasionally forming one large cluster as shown in the figure. Scale bar for (a)–(c) is 5 μm. (Image courtesy of Hideyuki Tanabe.)

Figure 4.

Visualization of centromeres in nuclei from different cell types. (a, b) View into the x,z plane of cuts through 3D reconstructions (volume rendering, Amira TGS software) of the spherical nucleus of a human lymphocyte (G0, a) and of the flat nucleus of a human fibroblast (G0, b). Centromeres are clustered at the nuclear periphery. The centromeres were visualized by 3DFISH with a pancentromeric (alphoid) probe. (c) 3D reconstruction (surface rendering, Amira TGS software) of simultaneously visualized territories and centromeres from chromosome 20 in the nucleus of a human lymphocyte (G0) combined with the partially reconstructed nuclear border. The centromeres are located at the nuclear periphery, while the chromatin bulk of the territories protrudes into the nuclear interior. (d–h) Mid‐optical sections through nuclei of human stimulated lymphocytes with immunostained kinetochores at different stages of the cell cycle. Note that centromeres (marked by kinetochores) have peripheral locations in early S phase and G0, while during early G1, late S and G2 stages they are often found more internally. Scale bars are 5 μm.



Abney JR, Cutler B, Fillbach ML, Axelrod D and Scalettar BA (1997) Chromatin dynamics in interphase nuclei and its implications for nuclear structure. Journal of Cell Biology 137: 1459–1468.

Alcobia I, Dilao R and Parreira L (2000) Spatial associations of centromeres in the nuclei of hematopoietic cells: evidence for cell‐type‐specific organizational patterns. Blood 95: 1608–1615.

Boyle S, Gilchrist S, Bridger JM, et al. (2001) The spatial organization of human chromosomes within the nuclei of normal and emerin‐mutant cells. Human Molecular Genetics 10: 211–219.

Brown KE, Amoils S, Horn JM, et al. (2001) Expression of α‐ and β‐globin genes occurs within different nuclear domains in haemopoietic cells. Nature Cell Biology 3: 602–606.

Brown KE, Baxter J, Graf D, Merkenschlager M and Fisher AG (1999) Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division. Molecular Cell 3: 207–217.

Cornforth MN, Greulich‐Bode KM, Bradford DL, et al. (2002) Chromosomes are predominantly located randomly with respect to each other in interphase human cells. Journal of Cell Biology 159: 237–244.

Cremer T and Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nature Reviews Genetics 2: 292–301.

Cremer M, von Hase J, Volm T, et al. (2001) Non‐random radial higher‐order chromatin arrangements in nuclei of diploid human cells. Chromosome Research 9: 541–567.

Ferguson M and Ward DC (1992) Cell cycle dependent chromosomal movement in pre‐mitotic human T‐lymphocyte nuclei. Chromosoma 101: 557–565.

Habermann F, Cremer M, Walter J, et al. (2001) Arrangements of macro‐ and microchromosomes in chicken cells. Chromosome Research 9: 569–584.

Kozubek S, Lúkasová E, Jirsová P et al. (2002) 3D Structure of the human genome: order in randomness. Chromosoma, published online 18 September 2002.

Manders EM, Kimura H and Cook PR (1999) Direct imaging of DNA in living cells reveals the dynamics of chromosome formation. Journal of Cell Biology 144: 813–821.

Martou G and De Boni U (2000) Nuclear topology of murine, cerebellar Purkinje neurons: changes as a function of development. Experimental Cell Research 256: 131–139.

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

Skalnikova M, Kozubek S, Lukasova E, et al. (2000) Spatial arrangement of genes, centromeres and chromosomes in human blood cell nuclei and its changes during the cell cycle, differentiation and after irradiation. Chromosome Research 8: 487–499.

Sun HB and Yokota H (1999) Correlated positioning of homologous chromosomes in daughter fibroblast cells. Chromosome Research 7: 603–610.

Tanabe H, Müller S, Neusser M, et al. (2002) Evolutionary conservation of chromosome territory arrangements in cell nuclei from higher primates. Proceedings of the National Academy of Sciences of the United States of America 99: 4424–4429.

Tumbar T and Belmont A (2001) Interphase movements of a DNA chromosome region modulated by VP16 transcriptional activator. Nature Cell Biology 3: 134–139.

Further Reading

Baxter J, Merkenschlager M and Fisher AG (2002) Nuclear organization and gene expression. Current Opinion in Cell Biology 14: 372–376.

Chevret E, Volpi EV and Sheer D (2000) Mini review: form and function in the human interphase chromosome. Cytogenetics and Cell Genetics 90: 13–21.

Cremer T, Kreth G, Koester H, et al. (2000) Chromosome territories, interchromatin domain compartment, and nuclear matrix: an integrated view of the functional nuclear architecture. Critical Reviews in Eukaryotic Gene Expression 12: 179–212.

Leitch AR (2000) Higher levels of organization in the interphase nucleus of cycling and differentiated cells. Microbiology and Molecular Biology Reviews 64: 138–152.

Parada LA and Misteli T (2002) Chromosome positioning in the interphase nucleus. Trends in Cell Biology 12: 425–432.

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Cremer, Marion, Schermelleh, Lothar, Solovei, Irina, and Cremer, Thomas(Jan 2006) Cell Cycle: Chromosomal Organization. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005769]