Hit-and-Run leaves its mark: Catalyst transcription factors and chromatin modification

Understanding how transcription factor (TF) binding is related to gene regulation is a moving target. We recently uncovered genome-wide evidence for a Hit-and-Run model of transcription. In this model, a master TF hits a target promoter to initiate a rapid response to a signal. As the hit is transient, the model invokes recruitment of partner TFs to sustain transcription over time. Following the run, the master TF hits other targets to propagate the response genome-wide. As such, a TF may act as a catalyst to mount a broad and acute response in cells that first sense the signal, while the recruited TF partners promote long-term adaptive behavior in the whole organism. This Hit-and-Run model likely has broad relevance, as TF perturbation studies across eukaryotes show small overlaps between TF-regulated and TF-bound genes, implicating transient TF-target binding. Here, we explore this Hit-and-Run model to suggest molecular mechanisms and its biological relevance.