Karen J. Meaburn and Tom Misteli
The natural habitat of eukaryotic genomes is the cell nucleus, where each chromosome is confined to a discrete region, referred to as a chromosome territory. This spatial organization is emerging as a crucial aspect of gene regulation and genome stability in health and disease.
What dochromosome territories look like?
The word ‘chromosome’ usually conjures up striking images of the dense, X-shaped entities seen during cell division. It is easy to forget that for most of the time chromosomes exist as unravelled structures and their arrangement is confined by the boundaries of the cell nucleus. We now know that each chromosome maintains its individuality during the cell cycle andoccupies a spatially limited volume, known as a chromosome territory. Using fluorescent tags, these can be seen in vivo as roughly spherical domains of about 2 micrometres in diameter (Fig. 1a, b; Box 1, overleaf). networks of channels. These make the genome sequences deep inside accessible to regulatory factors such as gene activators and inhibitors (Fig. 1c). In addition, the structure of the DNAwithin chromosome territories is nonrandom, as the chromosome arms are mostly kept apart from each other and gene-rich chromosome regions are separated from genepoor regions. This arrangement probably contributes to the structural organization of the chromosome, and might also help in regulating particular sets of genes in a coordinated manner. suggested (Fig. 1f). In addition, there is debateabout how chromatin fibres are organized at the surface of the chromosome territory. Some observations suggest that giant chromatin loops protrude from the chromosome territory and intermingle extensively with fibres from neighbouring chromosomes, whereas other studies seem to show that abutting chromosomes don’t mix much. Emerging high-resolution light-microscopy methods should settle this issuesoon.
Are the territories arranged in particular patterns within the nucleus?
Remarkably, yes. In lower eukaryotes such as plants and flies chromosomes tend to be polarized, with the ends of the arms (telomeres) on one side of the cell nucleus and the point at which the two arms meet (the centromere) on the opposite side. In mammalian cells, however, chromosome arrangement is more complex. Evenso, each chromosome can be assigned a preferential position relative to the nuclear centre, with particular chromosomes tending to be at the nuclear interior and others at the edge (Fig. 2a, overleaf). This preferential radial arrangement also, of course, gives rise to preferred clusters of neighbouring chromosomes.
So how does a chromosome fold up into this form?
This is not yet clear.Observations in plants suggest that the chromatin fibre — comprising the DNA and its associated proteins — forms large loops that are anchored to each other at their base (Fig. 1d). However, in higher eukaryotes such as mammals the fibre seems rather to be folded into distinct megabase-sized domains that are linked to one another (Fig. 1e). Each of these domains might represent a functional unit,because their replication is coordinated and maintained in consecutive cell cycles. A hybrid model in which smaller loops emanate from a central chromosome core has also been
Do all cells have them?
Chromosome territories can only form in cells that have a nucleus (eukaryotic cells), and most higher eukaryotes are thought to have them. But some lower eukaryotes, such as the yeast Saccharomycescerevisiae, lack chromosome territories and their chromosomes seem to be more loosely arranged.
Do the territories have an internal structure?
The interiors of chromosome territories are permeated by highly branched, interconnected
Figure 1 | Spatial organization in the nucleus. a, Territories can be visualized using chromosome-specific fluorescent probes. In this...