Involvement of promoter/enhancers in a feedback loop to regulate human gene expression.

The study described here was undertaken to extend the observation that some transcription factors can either stimulate or suppress gene expression depending on the local environment of their DNA binding site. It is suggested that if such transcription factors also had a mechanism to sense the expression level of the gene they control, then they could create a feedback loop able to keep expression of a gene within a limited range. The transcription factor would be activating if gene expression were determined to be too low and repressing if it were too high. To test the above idea, I have examined the effect of gene expression on the ability of the transcription factor binding areas, the promoter/enhancers, to stimulate or attenuate gene expression depending on the existing expression level of a gene. Studies were carried out with a population of 61 human genes expressed selectively in liver. A similar study was carried out with thyroid genes. The total length of all promoter/enhancers in each gene sequence was determined and compared in weakly and strongly expressed genes. The results showed that the level of expression was stimulated by promoter/enhancers in weakly expressed genes and antagonized in strongly expressed ones. The results are interpreted to indicate that promoter/enhancers act to keep expression of a gene within a defined range that is appropriate for the gene's function.