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.

Bacterial degrons in synthetic circuits

“…The first intrinsic sequences used in complex synthetic circuits were MarA, MarAn20 and RepA70 (also called RepAn70) [43,49]. MarA is a transcription factor that regulates multiple genes involved in antibiotic-resistance pathways [128], and the N-terminus of MarA is a target of Lon [129]. The MarAn20 tag is the last 20 amino acid tag from the N-terminal of MarA.…”