Chromatin Can move to Specific Sites within the Nucleus to Alter gene Expression
A variety of different types of experiments has led to the conclusion that the position of a gene in the interior of the nucleus changes when it becomes highly expressed. Thus, a region that becomes very actively transcribed is sometimes found to extend out of its chromosome territory, as if in an extended loop (Figure 4–56). We will see in Chapter 6 that the initiation of transcription—the first step in gene expression—requires the assembly of over 100 proteins, and it makes sense that this would be facilitated in regions of the nucleus enriched in these proteins.
More generally, it is clear that the nucleus is very heterogeneous, with functionally different regions to which portions of chromosomes can move as they are subjected to different biochemical processes—such as when their gene expression changes. It is this issue that we discuss next.
Figure 4–55 A fractal globule model for interphase chromatin. An extension of the 3C method in Figure 4–48, called Hi-C, was used to measure the extent to which each of the three thousand 1 mb segments in the human genome was located adjacent to any other of these segments. The results support the type of model shown. In the enlarged fractal globule illustrated, a region of 5 million base pairs is seen to fold in a way that keeps regions that are neighbors along the one-dimensional DNA helix as neighbors in three dimensions; this gives rise to monochromatic blocks in this representation that are obvious both on the surface and in cross section. The fractal globule is a knot-free conformation of the DNA that permits dense packing, yet retains an ability to easily fold and unfold any genomic locus. (Adapted from
E. lieberman-Aiden et al., Science 326:289–293, 2009. with permission  from AAAS.)
Figure 4–56 An effect of high levels of gene expression on the intranuclear location of chromatin. (A) Fluorescence micrographs of human nuclei showing how the position of a gene changes when it becomes highly transcribed. The region of the chromosome adjacent to the gene (red) is seen to leave its chromosomal territory (green) only when it is highly active. (b) Schematic representation of a large loop of chromatin that expands when the gene is on, and contracts when the gene is off. Other genes that are less actively expressed can be shown by the same methods to remain inside their chromosomal territory when transcribed. (From J.R. Chubb and w.A. bickmore, Cell 112:403–406, 2003. with permission from Elsevier.)
Networks of macromolecules Form a Set of Distinct biochemical Environments inside the Nucleus
In Chapter 6, we shall describe the function of a variety of subcompartments that are present within the nucleus. The largest and most obvious of these is the nucleolus, a structure well known to microscopists even in the nineteenth century (see Figure 4–9). The nucleolus is the cell’s site of ribosome subunit formation, as well as the place where many other specialized reactions occur (see Figure 6–42): it consists of a network of RNAs and proteins concentrated around ribosomal RNA genes that are being actively transcribed. In eukaryotes, the genome contains multiple copies of the ribosomal RNA genes, and although they are typically clustered together in a single nucleolus, they are often located on several separate chromosomes.
A variety of less obvious organelles are also present inside the nucleus. For example, spherical structures called Cajal bodies and interchromatin granule clusters are present in most plant and animal cells (Figure 4–57). Like the nucleolus, these organelles are composed of selected protein and RNA molecules that bind together to create networks that are highly permeable to other protein and RNA molecules in the surrounding nucleoplasm.