Active degradation of a regulator controls coordination of downstream genes

Abstract

Several key transcription factors have unusually short half-lives compared to other cellular proteins. Here, we explore the utility of active degradation in shaping how a master regulator coordinates its downstream targets. We focus our studies on the multi-antibiotic resistance activator MarA, which controls a variety of stress response genes in Escherichia coli. We modify its half-life either by knocking down the protease that targets it via CRISPRi or by engineering MarA to protect it from degradation. Our experimental, analytical, and computational results indicate that active degradation can impact both the rate of coordination and the maximum coordination that downstream genes can achieve. Trade-offs between these properties show that perfect information fidelity and instantaneous coordination cannot coexist.