Are less active chromosomes like WD40?

PLoSBiol3.5.Fig1bNucleus46ChromosomesWe all have 46 chromosomes worth of DNA in each of our cells. Each one is kind of a stringy object that is typically around a few micrometres across, and all 46 are squeezed into a cell nucleus that is itself maybe only 7 micrometres across. These chromosomes are surprisingly variable. Chromosome number 18 has maybe 250 genes on it, while number 19 has around 1,500 genes, despite being around the same size*. So chromosome 19 is a lot more active than 18, many more proteins are being made from its much larger number of genes.

It has been known for a long time that the chromosomes are not uniformly distributed in the nucleus. The active ones, the ones like chromosome 19 with many genes, tend to be nearer the centre, while the quieter ones are near the edge. You can see this in image and schematic at top left, the less active chromosome 18 is at the bottom near the right end, while the more active chromosome 19 is above it and so away from the edge. The image is a from a paper by Bolzer et al.

This begs the question: Why? What is the mechanism for this separation? Does it have a biological function? I can’t answer that last question but it may be possible to at least construct a model to reproduce this segregation of the less active chromosomes to the edge of the nucleus.

If the activity of chromosomes is cooperative, in the sense that when two active gene-rich regions are close they tend to work together and to stick together, then this will make the regions of DNA with few genes segregate from those with many genes. It will also tend to make the chromosomes with many genes move to the centre, while pushing the less active ones to the outside of the nucleus – just what is observed.

This can be understood as such a cooperativity looks just like the attractions between molecules that causes liquids to condense from vapours, and that causes WD40 and water to separate – to not mix. Water molecules attract each other more than they do the oil molecules in WD40. This is not only means WD40 and water don’t mix, it also causes effects at surfaces, such as the fact that WD40 will spread as a film on metal even under water – which is why WD40 will loosen jammed metal even immersed in water.

All you need to assume is this cooperativity, and then there is a strong analogy to water and oil, even at surfaces. However, this cooperativity is an assumption, one that may or may not be true. In these circumstances maybe it is just best to just run with it, and see where it works, and where it fails.

*Some chromosomes are bigger than others. Chromosome 1, the biggest has about 4 times the DNA of 18 or 19.

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