Chromosome topology in mammalian interphase nuclei.

Since 1968, when Comings published the pioneering paper on "the rationale for an ordered arrangement of chromatin in the interphase nucleus," technical methods have progressed tremendously and improved our understanding of interphase organization. The existence of highly ordered organizational patterns of the cell nucleus appears to be beyond any doubt and it is difficult to escape the conclusion that interphase chromosome topology is important for the complex regulation of the many varied and interrelated nuclear processes. However, it is worth emphasizing that a universally valid principle of chromosome arrangement does not exist and, therefore, any generalization of interphase patterns can be misleading. The factors of order according to which the chromosomes are arranged inside the nucleus are manifold: (1) Individual chromosomes remain in spatially separated domains throughout interphase, preventing an intermingling of the decondensed euchromatin. (2) Chromosome regions that contain constitutive heterochromatin associate into larger chromocenters. (3) In most cell types direct associations between interphase domains of homologous chromosomes are not observed. In others homologous heterochromatic regions tend to be paired preferentially. (4) Interphase chromosomes do not float freely in the nucleoplasm; they are associated to varying degrees with the nuclear membrane and other components of the nuclear scaffold. The number of attachment sites for each chromosome to the nuclear membrane is relatively low. (5) The positions of centromeres (and pericentromeric heterochromatin) are nonrandom and characteristic of each cell type. Specific centromere movements occur during the cell cycle, during differentiation, and under certain pathophysiological conditions. (6) The telomeric chromosome ends are particularly prone to associate in certain somatic cell types and in meiotic prophase cells. (7) The arrangement of repetitive DNA families appears to determine a structural framework of the interphase nucleus. Different cell types of one organism can exhibit marked differences in their repetitive DNA framework, whereas cells that are in an identical differentiated state or an identical phase of the cell cycle often show comparable interphase patterns even in evolutionarily distant species. (8) The various steps of ribosome biogenesis take place in a precise fashion within a separate nuclear domain, the nucleolus. The topologically well-defined nucleolar substructures are required for rDNA transcription and pre-rRNA processing. (9) A compartmentalization of transcriptional and processing events is also evident in the rest of the nucleus. However, it is not yet known if the in situ sites of transcription and RNA processing for a particular (nonribosomal) gene or gene family are actually adjacent. (10) DNA replication is precisely spatiotemporally regulated within the nucleus. The replication domains are immobilized on the nuclear matrix.(ABSTRACT TRUNCATED AT 400 WORDS)