We demonstrate that the nuclear topological arrangement of chromosome territories (CTs) has been conserved during primate evolution over a period of about 30 million years. Recent evidence shows that the positioning of chromatin in human lymphocyte nuclei is correlated with gene density. For example, human chromosome 19 territories, which contain mainly gene-dense and early replicating chromatin, are located toward the nuclear center, whereas chromosome 18 territories, which consist mainly of genepoor and later replicating chromatin, is located close to the nuclear border. In this study, we subjected seven different primate species to comparative analysis of the radial distribution pattern of human chromosome 18-and 19-homologous chromatin by three-dimensional fluorescence in situ hybridization. Our data demonstrate that gene-density-correlated radial chromatin arrangements were conserved during higher-primate genome evolution, irrespective of the major karyotypic rearrangements that occurred in different phylogenetic lineages. The evolutionarily conserved positioning of homologous chromosomes or chromosome segments in related species supports evidence for a functionally relevant higher-order chromatin arrangement that is correlated with gene-density.
In spite of strong evidence that the nucleus is a highly organized organelle, a consensus on basic principles of the global nuclear architecture has not so far been achieved. The chromosome territory-interchromatin compartment (CT-IC) model postulates an IC which expands between chromatin domains both in the interior and the periphery of CT. Other models, however, dispute the existence of the IC and claim that numerous chromatin loops expand between and within CTs. The present study was undertaken to resolve these conflicting views. (1) We demonstrate that most chromatin exists in the form of higher-order chromatin domains with a compaction level at least 10 times above the level of extended 30 nm chromatin fibers. A similar compaction level was obtained in a detailed analysis of a particularly gene-dense chromosome region on HSA 11, which often expanded from its CT as a finger-like chromatin protrusion. (2) We further applied an approach which allows the experimental manipulation of both chromatin condensation and the width of IC channels in a fully reversible manner. These experiments, together with electron microscopic observations, demonstrate the existence of the IC as a dynamic, structurally distinct nuclear compartment, which is functionally linked with the chromatin compartment.
A gene density–related difference in the radial arrangement of chromosome territories (CTs) was previously described for human lymphocyte nuclei with gene-poor CT #18 located toward the nuclear periphery and gene-dense CT #19 in the nuclear interior (Croft, J.A., J.M. Bridger, S. Boyle, P. Perry, P. Teague, and W.A. Bickmore. 1999. J. Cell Biol. 145:1119–1131). Here, we analyzed the radial distribution of chromosome 18 and 19 chromatin in six normal cell types and in eight tumor cell lines, some of them with imbalances and rearrangements of the two chromosomes. Our findings demonstrate that a significant difference in the radial distribution of #18 and #19 chromatin is a common feature of higher order chromatin architecture in both normal and malignant cell types. However, in seven of eight tumor cell lines, the difference was less pronounced compared with normal cell nuclei due to a higher fraction of nuclei showing an inverted CT position, i.e., a CT #18 located more internally than a CT #19. This observation emphasizes a partial loss of radial chromatin order in tumor cell nuclei.
G-and R-bands of metaphase chromosomes are characterized by profound differences in gene density, CG content, replication timing, and chromatin compaction. The preferential localization of gene-dense, transcriptionally active, and early replicating chromatin in the nuclear interior and
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