Paper

Single-cell Analysis of Attenuation-Driven Transcription Reveals New Principles of Bacterial Gene Regulation

Ali, N, Engl, C, Ribeiro, AS, Jagadeesan, R, Moradian, S, Behrends, V

2025

Overview

Transcription attenuation fine-tunes biosynthetic gene expression in bacteria via premature termination upon metabolic signals. In transcription initiation-controlled bacterial systems, promoter architecture and transcription factor binding sets the size of transcriptional bursts at σ70 promoters, while distal enhancer elements and associated transcriptional activators modulate burst frequency at σ54 promoters. Using the tryptophan biosynthesis operon as a model, we show that transcription attenuation, acting post-initiation and alongside transcriptional repression, simultaneously modulates both burst size and frequency from a σ70 promoter. This challenges the view that frequency modulation requires distal enhancer input and reveals that post-initiation mechanisms can shape divergent transcriptional bursting. We also uncover that bacteria use cross-feeding as a previously unrecognised strategy for controlling cell-to-cell variation in gene expression, with implications for metabolic coordination among cells. These findings redefine transcription dynamics within cell populations and suggest new principles by which bacteria regulate gene expression to adapt to environmental change.

• Publisher: Cold Spring Harbor Laboratory
• Subject: Microbiology