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Eukaryotic transcription generally occurs in bursts of activity lastingminutes to hours; however, state-of-the-art measurements have revealed thatmany of the molecular processes that underlie bursting, such as transcriptionfactor binding to DNA, unfold on timescales of seconds. This temporaldisconnect lies at the heart of a broader challenge in physical biology ofpredicting transcriptional outcomes and cellular decision-making from thedynamics of underlying molecular processes. Here, we review how new dynamicalinformation about the processes underlying transcriptional control can becombined with theoretical models that predict not only averaged transcriptionaldynamics, but also their variability, to formulate testable hypotheses aboutthe molecular mechanisms underlying transcriptional bursting and control.

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