8.2 Chromosome scaffolds
Most of the chromosomal DNA chains within the interphase nucleus are believed to be held on a scaffold or backbone structure made from various proteins, with loops of between 20 and 200 kb extruding from attachment sites. This chromosome structure is shown schematically in Figure 40. The scaffold, as well as permitting further compaction, serves to bring the DNA together in organised regions. There are many different protein components of these scaffolds, amongst them DNA topoisomerases.
How might DNA topoisomerases be involved in regulating the chromatin structure in loops?
DNA topoisomerases cut the DNA backbone and allow the strands to rotate around the helical axis, resulting in the addition or removal of DNA twists. The action of this enzyme could therefore result in relaxation or compaction of individual loops through the introduction or removal of supercoils.
Compaction is also influenced by the status of the histone tail modifications. As an example, remember that the addition of an acetyl group to lysine residues effectively removes their positive charge, reducing the ability of the histone tails to interact with the DNA backbone and thereby hindering compaction. Thus histone modification and topoisomerase activity can regulate the activity of genes in a looped region and thus regulate genes across longer stretches of DNA. These regions of chromatin are referred to as domains. An additional important implication of this scaffolding arrangement is that the action of topoisomerases and ensymes that modify chromatin could alter the compaction of individual loops without affecting neighbouring domains, as shown in Figure 40.
Finally, if you now look back at Figure 12, you can also see why transcriptionally active regions flanked by attachment sites need topoisomerase activity to release the torsional stresses that build up ahead of the transcription complex.
In most cases, visualising such scaffold and loop structures with the light microscope is impossible, due to the limited resolution and the diffuse nature of the DNA. However, it is possible, even at the light microscope level, to see such arrangements in the so-called lamp brush chromosomes in the developing amphibian oocyte (egg cell). The DNA in these cells is highly transcriptionally active as the oocyte is synthesizing large stores of protein. If you look at the example in Figure 41, you can see large loops extending out from a scaffold-like structure.