(75a) Construction of Genetic Devices By Engineering Transcriptional Interference

Different levels of gene expression are often obtained by the action of transcription factors in the cis‑regulatory region. Transcriptional interference is a mechanism where a transcriptional process is negatively affected by the presence of neighboring proteins on the same DNA region. Therefore, Transcriptional Interference offers a promising mechanism for building elements for the design of tunable gene regulation. Here we use tandem regulatory elements in the cis-regulatory region that are susceptible to Transcriptional Interference. By tweaking the characteristics of each regulatory element, the extent of Transcriptional Interference on each other can be engineered thus modifying aspects of the gene expression response such as overall regulatory range, sharpness of the induction curve for each inducer as well as sensitivity to each of the inducers. Such behaviors are successfully described by a mathematical model of Transcriptional Interference, presenting the opportunity to both understand how naturally occurring systems integrate multiple inputs exerted by tandem transcription factors and how this type of systems can be engineered de novo.