8.3 Chromosome distribution within the nucleus

DNA from any one particular chromosome is a single chain, many millions of bases long, and this chain is attached to a scaffold structure. It is not surprising then, that if we examine the interphase nucleus, each chromosome is seen to fill a localised area. This localised distribution of individual chromosomes is illustrated in Figure 42 with an examination of human chromosomes within the interphase nucleus. In these examples, special DNA probes have been used to detect the location of the entire chromosome by FISH (Subsection 2.4). This technique is known as chromosome painting. In Figure 42a, several different chromosomes are visualised using fluorescently tagged DNA from the whole chromosome as probes. As you can see, each chromosome is located within a defined area.

In order to explore a single human chromosome in more detail, a particular combination of DNA probes for different stretches along a single chromosome has been used, each probe being labelled with a different fluorophore (Figure 42b). In this way, the relative position of subsections of the chromosome can be determined. In the example in Figure 42b, DNA probes corresponding to different areas of human chromosome 5 have been used. As you can see, each copy of chromosome 5 is present within a very restricted area. Note also that the order of the colours on chromosome 5 in the interphase nucleus is the same as that on the mitotic chromosome shown alongside.

Figure 42 Organisation of DNA and localisation of chromosomes in the human male interphase nucleus. (a) FISH using whole chromosome ‘paints’ for various chromosomes. All the nuclei are counterstained blue and chromosomes are stained red or green (from Boyle et al., 2001). Different pairs of chromosomes are stained in each image. In the bottom right image, the single Y chromosome is stained. (b) FISH using specific probes for discrete regions of chromosome 5 to detect the linear organisation of both chromosomes in the diploid interphase nucleus. A mitotic (metaphase) chromosome is indicated alongside (lower right, boxed). Notice that the pattern of colours in the chromosomes is the same in both interphase and metaphase.

Long description

A further aspect of chromosomal localisation is that some areas of individual chromosomes appear to be associated with specific areas of the nucleus in accordance with their transcriptional activity. For example, telomeres and many genes that are transcriptionally silent are often located in the nuclear periphery, or edge of the nucleus. Genes that are highly transcribed, such as those involved in ribosomal RNA synthesis, are located in the nucleolus, a spherical body within the nucleus.