Transcription factor binding kinetics and transcriptional bursting: What do we really know?

In eukaryotes, transcription is a discontinuous process with mRNA being generated in bursts, after the binding of transcription factors (TFs) to regulatory elements on the genome. Live-cell single-molecule microscopy has highlighted that transcriptional bursting can be controlled by tuning TF/DNA binding kinetics. Yet the timescales of these two processes seem disconnected with TF/DNA interactions typically lasting orders of magnitude shorter than transcriptional bursts. To test models that could reconcile these discrepancies, reliable measurements of TF binding kinetics are needed, also accounting for the current limitations in performing these single-molecule measurements at specific regulatory elements. Here, we review the recent studies linking TF binding kinetics to transcriptional bursting and outline some current and future challenges that need to be addressed to provide a microscopic description of transcriptional regulation kinetics.