Avoiding transcription factor competition at promoter level increases the chances of obtaining oscillation

It has been emphasized in the literature that the architecture of a genetic oscillator must include positive (activating) and negative (inhibiting) genetic interactions in order to yield robust oscillations. Our results point out that the oscillatory capacity is not only affected by the interaction polarity but by how it is implemented at promoter level. For a chosen oscillator architecture, we show by means of numerical simulations that the existence or lack of competition between activator and inhibitor at promoter level affects the probability of producing oscillations and also leaves characteristic fingerprints on the associated period/amplitude features.In comparison with non-competitive binding at promoters, competition drastically reduces the region of the parameters space characterized by oscillatory solutions. Moreover, while competition leads to pulse-like oscillations with long-tail distribution in period and amplitude for various parameters or noisy conditions, the non-competitive scenario shows a characteristic frequency and confined amplitude values. Our study also situates the competition mechanism in the context of existing genetic oscillators, with emphasis on the Atkinson oscillator.In the relatively young field of synthetic biology [1,2], there is increasing interest in the conception and construction of genetic circuits that are reliable with respect to their designed function. Having given the first step with the implementation of biological switches [3], the next step for synthetic biology was the construction of biological oscillators. The first successful implementation [4] constituted the onset of the quest for oscillators of tunable amplitude and/or period. Oscillators are important in biology for many reasons, since they are involved in the cell cycle, cell motion, embryonic development [5]. In some cases, the genetic machinery associated with the oscillatory behavior is rather small.In the context of genetic designs, two- and three-elemen