How gene expression and internal state interact

Gene expression and its control form a large part of modern molecular biology and are directly relevant to our definition of "livingness". By changing the genes that it expresses, a cell alters its internal state. The alteration might be trivial: a mere re-adjustment, returning the cell to a status quo that has been transiently upset. But it might be radical, a dramatic change in appearance and behaviour.

Two of the questions arising from chapter 7 now become prominent:-

  • If the expression of a gene is controlled by transcription factors, why do these factors work some of the time but not all the time?
  • Suppose a gene is switched off, for instance by a repressor. What switches it on again exactly when the cell needs it, no earlier and no later?

There is a single general answer to both questions: proteins, including transcription factors and repressors, can be modified. Modification of a repressor or a transcription factor might prevent DNA binding; alternatively, DNA binding might not be possible without modification. Modification of transcription factors and repressors ensures that the cell expresses the right genes at the right times. (Also, protein synthesis can be regulated at levels other than gene transcription: processing of the messenger after transcription; messenger transport from nucleus to cytoplasm; and translation by the ribosomes. Moreover, the life-span of the messenger in the cytoplasm can sometimes be altered. But although these levels of control are significant, we shall ignore them here; it is control of transcription that primarily determines whether a particular protein is made. If we discussed the other mechanisms it would complicate the picture.)

Suppose the cell takes in a large quantity of a particular nutrient, such as glucose. This happens in your liver cells after you have eaten a meal. Enzymes that convert the nutrient into storage form (e.g. glucose into glycogen) have suddenly become necessary. One way to meet this need is to accelerate the transcription of the genes encoding these enzymes. This acceleration is achieved by modifying the regulatory proteins, and the modifier might be the nutrient molecule itself. Fig. 8-1 shows a hypothetical scheme of this kind.

initiation complex

Fig. 8-1: illustration of how gene expression can be controlled. In this hypothetical example, nutrient molecules increase the rate of production of an enzyme that puts the nutrient into storage.

In this scheme, a nutrient molecule binds the repressor, causing it to detach from the DNA. This allows the gene for the storage enzyme to be transcribed. Another nutrient molecule binds to a transcription factor, enabling it to bind to its enhancer. The bound transcription factor activates the initiation complex, accelerating transcription. Rapid messenger RNA production ensues, the requisite enzyme is made, and many millions of nutrient molecules are put into storage as required. When nearly all the nutrient has been converted to storage form, its level in the cell is consequently much lower. So there is no longer enough free nutrient to bind the transcription factor or the repressor. The transcription factor therefore becomes detached from the enhancer and ceases to function. The repressor binds to the promoter again. Transcription stops; production of the messenger RNA for the enzyme ceases.

initiation complex

Fig. 8-1: illustration of how gene expression can be controlled. In this hypothetical example, nutrient molecules increase the rate of production of an enzyme that puts the nutrient into storage.

This hypothetical example illustrates how the mechanisms we discussed in chapter 7 can be used to turn gene expression on and off. However, mechanisms of this kind only preserve the cell's internal state. They ensure that the cell's overall behaviour is more or less unchanged despite a large perturbation, such as a sudden influx of nutrient molecules. This extends the idea of homeostasis that we introduced in chapter 6. Changes in gene expression that resist changes in the internal state are fundamental to cellular homeostasis.

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