Dual-promoter control of gene expression: from transcriptional fine-tuning to antibiotic resistance

The first and arguably most critical level of gene expression is transcription of the genetic information from DNA into RNA. Within this process, transcription initiation stands out as the key step that influences all downstream events. Central to initiation are promoters, DNA sequences that interact with the key enzyme of transcription, RNA polymerase. A single transcription unit may be controlled by one or multiple promoters, a strategy found across all domains of life. This review highlights how combinatorial promoter arrangements control gene expression in microorganisms, with brief comparisons to other organisms. We also explore how these promoter architectures function as sensors for stress-related molecules, such as antibiotics. We examine how these insights can be applied to predict previously unidentified mechanisms of antibiotic resistance. Finally, the use of dual-promoters in synthetic biology is outlined and discussed.