Transcriptional Regulation by Competing Transcription Factor Modules

@article{citeulike:997773, abstract = {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 input\&\#8211;output 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.}, author = {Hermsen, Rutger and Tans, Sander and Ten}, citeulike-article-id = {997773}, doi = {10.1371/journal.pcbi.0020164}, journal = {PLoS Computational Biology}, keywords = {regulation, transcription}, month = {December}, number = {12}, pages = {e164+}, posted-at = {2007-04-16 14:10:54}, priority = {1}, title = {Transcriptional Regulation by Competing Transcription Factor Modules}, url = {http://dx.doi.org/10.1371/journal.pcbi.0020164}, volume = {2}, year = {2006} }

TY - JOUR ID - citeulike:997773 L3 - citeulike-article-id:997773 TI - Transcriptional Regulation by Competing Transcription Factor Modules JF - PLoS Computational Biology VL - 2 IS - 12 SP - e164 N2 - 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 input–output 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. KW - regulation KW - transcription AU - Hermsen, Rutger AU - Tans, Sander AU - Ten PY - 2006/12/01/ UR - http://dx.doi.org/10.1371/journal.pcbi.0020164 ER -