Some genes are known to produce proteins that repress their own expression. FoxA, which has a role in the endo-mesoderm specification, is such a gene.
If, for some reason, the input to a gene (i.e. the transcription factor concentrations that determine its expression level) is noisy, auto-inhibition may help to stabilise the expression level. When gene expression goes up, the concentration of the inhibitor goes up, repression increases, and the expression goes down. On the other hand, when expression decreases, the inhibitor concentration decreases as well, and gene expression rises. However, there is a certain delay between cause and effect in this type of regulation. This means, for instance, that a gene will initially produce more inhibitor than it needs to reach a final stable expression level. After a while, the inhibitor level has increased so much that gene expression decreases below the stable level, etc. etc. Under some conditions this overshooting and undershooting peters out, and the expression reaches a steady state. However, under other conditions the oscillations are self-sustaining, and, if nothing else changes, go on forever (see also the Simple Negative Feedback page in the Theory section). These effects can all be simulated in NetBuilder.
The gene in this picture produces its own repressor. The diamond-shaped symbol represents the protein product - which may be monomeric (in which case the associated power parameter P is 1) or homo-oligomeric (then P > 1). The blue triangle is a 'driver' transcription factor, which is used to change the gene expression level. The graph below shows what happens to the gene expression level (in red) when the concentration of the driver transcription factor (the blue line) changes from 0 to 1 (which means that the occupation of its binding site changes from 0 to 50%). The behaviour represented by the thick red line is observed for a monomeric inhibitor (P = 1), the thin red line shows the effect of an oligomeric suppressor (P = 4). The associated multiplication factor F of the gene is 10. The picture clearly show that this auto-inhibitory system can, under particular conditions, reach a stable steady state.
The results of a further investigation into the behaviour of this system is found on the next page.
Last modified by MJS on Thursday March 28, 2002