(188m) Construction of Genetic Logic Gates Using Transcriptional Interference

Different levels of gene expression are often obtained by the action of transcription factors in the cis‑regulatory region. Transcriptional interference (TI) is a mechanism where a transcriptional process is negatively affected by the presence of neighboring proteins on the same DNA region. Therefore, TI offers a promising mechanism for building elements for the design of tunable gene regulation. Here we have created AND, OR, NAND, NOR and XOR logic gates making use solely of TI. By tweaking the characteristics of each regulatory element, the extent of TI 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 TI, presenting the opportunity to both understand how naturally occurring systems integrate multiple inputs exerted by transcription factors and how this type of systems can be engineered de novo.