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 beca use of the technical difficulties inherent in analyzing the mechanics of a 2.5 MDa complex comprising greater than 50 polypeptide components. To compl ement the biochemical approach we have employed mathematical modeling as a means to understand the mechanism of synergy. Parameters relevant to activa ted transcription were varied in a simple biochemical system and the data w ere compared to the transcriptional response predicted by a multi-component statistical model. We found that the model achieved a consistent, semi-qua ntitative 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 cooperativ ity in the activation process beyond what would be predicted from one curre nt model suggesting that activators function solely by simple recruitment o f the general transcription machinery to the promoter. (C) 1999 Academic Pr ess.