A matter of time: Using dynamics and theory to uncover mechanisms of transcriptional bursting

Eukaryotic transcription generally occurs in bursts of activity lasting minutes to hours; however, state-of-the-art measurements have revealed that many of the molecular processes that underlie bursting, such as transcription factor binding to DNA, unfold on timescales of seconds. This temporal disconnect lies at the heart of a broader challenge in physical biology of predicting transcriptional outcomes and cellular decision-making from the dynamics of underlying molecular processes. Here, we review how new dynamical information about the processes underlying transcriptional control can be combined with theoretical models that predict not only averaged transcriptional dynamics, but also their variability, to formulate testable hypotheses about the molecular mechanisms underlying transcriptional bursting and control.