Date Published:

Abstract:

Author summary Genes differ in the frequency at which they are expressed and in the form of regulation used to control their activity. The basic level of regulation is mediated by different types of DNA-binding proteins, where each type regulates particular gene(s). We distinguish between two basic forms of regulation: positive—if a gene is activated by the binding of its regulatory protein, and negative—if it is active unless bound by its regulatory protein. Due to the multitude of genes and regulators, spurious binding and unbinding events, called “crosstalk”, could occur. How does the form of regulation, positive or negative, affect the extent of regulatory crosstalk? To address this question, we used a mathematical model integrating many genes and many regulators. As intuition suggests, we found that in most of the parameter space, crosstalk increased with the availability of regulators. We propose, that crosstalk is usually reduced when networks are designed such that minimal regulation is needed, which we call the ‘idle’ design. In other words: a frequently needed gene will use negative regulation and conversely, a scarcely needed gene will employ positive regulation. In both cases, the requirement for the regulators is minimized. In addition, we demonstrate how crosstalk can be calculated from available datasets and discuss the technical challenges in such calculation, specifically data incompleteness.

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