Gene
regulatory networks lie at the heart of cellular computation. In these networks, intracellular and extracellular signals are integrated by
transcription factors, which control the expression of transcription units by binding to
cis-regulatory regions on the DNA. The designs of both eukaryotic and prokaryotic cis-regulatory regions are usually highly complex. They frequently consist of both repetitive and overlapping transcription factor binding sites. To unravel the
design principles of these
promoter architectures, we have designed in silico prokaryotic transcriptional logic gates with predefined inputoutput relations using an evolutionary algorithm. The resulting cis-regulatory designs are often composed of
modules that consist of tandem arrays of binding sites to which the transcription factors bind cooperatively. Moreover, these modules often overlap with each other, leading to competition between them. Our analysis thus identifies a new signal integration motif that is based upon the interplay between intramodular cooperativity and intermodular competition. We show that this signal integration mechanism drastically enhances the capacity of cis-regulatory domains to integrate signals. Our results provide a possible explanation for the complexity of promoter architectures and could be used for the rational design of synthetic gene circuits.
More abstracts about the Transcriptional Regulation by Competing Transcription Factor Modules