A mathematical model for synergistic eukaryotic gene activation

The precise biochemical mechanism underlying the synergistic action of gene activators on eukaryotic transcription has eluded a solution, largely because of the technical difficulties inherent in analyzing the mechanics of a 2.5 MDa complex comprising greater than 50 polypeptide components. To complement the biochemical approach we have employed mathematical modeling as a means to understand the mechanism of synergy. Parameters relevant to activated transcription were varied in a simple biochemical system and the data were compared to the transcriptional response predicted by a multi-component statistical model. We found that the model achieved a consistent, semi-quantitative description of the measured transcriptional response, and enabled the characterization and measurement of thermodynamic parameters in the in vitro system. The results provide evidence for the existence of cooperativity in the activation process beyond what would be predicted from one current model suggesting that activators function solely by simple recruitment of the general transcription machinery to the promoter. (C) 1999 Academic Press.