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We study the effects of multiple binding sites in the promoter of a geneticoscillator. We evaluate the regulatory function of a promoter with multiplebinding sites in the absence of cooperative binding, and consider differenthypotheses for how the number of bound repressors affects transcription rate.Effective Hill exponents of the resulting regulatory functions reveal anincrease in the nonlinearity of the feedback with the number of binding sites.We identify optimal configurations that maximize the nonlinearity of thefeedback. We use a generic model of a biochemical oscillator to show that thisincreased nonlinearity is reflected in enhanced oscillations, with largeramplitudes over wider oscillatory ranges. Although the study is motivated bygenetic oscillations in the zebrafish segmentation clock, our findings mayreveal a general principle for gene regulation.

Nonlinearity arising from noncooperative transcription factor binding enhances negative feedback and promotes genetic oscillations