Time will tell: comparing timescales to gain insight into transcriptional bursting.

Recent quantitative measurements have revealed dynamics of transcription factor DNA binding, preinitiation complex assembly, chromatin remodeling, and transcriptional bursting in living cells. Timescale comparison between transcription initiation events (input) and transcriptional burst kinetics (output) reveals mechanisms of transcription regulation. Transcription dynamics are shaped by the complex interplay of transient DNA binding of regulatory factors and the local environment (chromatin, clustering of regulatory factors, and enhancer–promoter interactions). Emerging imaging technologies are beginning to facilitate the dissection of input–output relationships at single genes to understand how regulatory factors affect rate-limiting steps. Recent imaging studies have captured the dynamics of regulatory events of transcription inside living cells. These events include transcription factor (TF) DNA binding, chromatin remodeling and modification, enhancer–promoter (E–P) proximity, cluster formation, and preinitiation complex (PIC) assembly. Together, these molecular events culminate in stochastic bursts of RNA synthesis, but their kinetic relationship remains largely unclear. In this review, we compare the timescales of upstream regulatory steps (input) with the kinetics of transcriptional bursting (output) to generate mechanistic models of transcription dynamics in single cells. We highlight open questions and potential technical advances to guide future endeavors toward a quantitative and kinetic understanding of transcription regulation. [ABSTRACT FROM AUTHOR]