Chong, S. et al. Cell 158, 314–326 (2014).

Transcription of highly expressed genes has been found to occur in stochastic bursts, a scheme thought to play an evolutionary role in maintaining population diversity. In order to understand the mechanism behind this phenomenon in bacteria, Chong et al. applied single-molecule methods. To monitor transcription elongation in real time, they used a fluorogenic RNA stain and, using total-internal-reflection fluorescence microscopy, recorded time-lapse movies of nascent mRNAs being produced on hundreds of single, immobilized DNA templates. This in vitro approach, along with a live-cell mRNA fluorescence in situ hybridization assay, allowed them to observe that a buildup of positive DNA supercoiling slows down and eventually halts transcription elongation, but gyrase binding to supercoiled DNA restarts transcription. Chong et al. concluded that supercoiling dynamics caused by gyrase association and dissociation are responsible for transcriptional bursting in bacteria.