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

Abstract

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.

Keywords: TF binding; dynamic regulation; gene regulatory networks; transcriptional model; transcriptional regulation; “Hit-and-Run”.

Figure 1

“Hit‐and‐Run” transcription: A proposed mechanism to explain how transcription initiated by the bZIP1 transient “hit”, can continue after the “catalyst TF” “runs” off to its next target 7. Our hypothesis in this essay proposes that when bZIP1 transiently “hits” a target, it recruits a chromatin modifier, Histone Acetyl Transferase (HAT complex) (Panel A). Next, the HAT complex acetylates histones associated with the promoter of bZIP1 transient targets (Panel B). This histone acetylation at the transcription start site (TSS) of the promoter region can provide accessibility for partner TFs, which would enable transcription of the transient bZIP1 targets to continue after the “catalyst TF” moves on to its next target (the “run”) (Panel C). In the specific example of bZIP1 7, along with the known bZIP binding site (G‐box 12), other cis‐elements including W‐Box and I‐Box motifs are over‐represented in the promoters of hit‐and‐run targets. These additional cis‐motifs were previously shown to bind WRKY 41 and MYB 42 TFs respectively, implicating bZIP1 “partners” involved in continued transcription after bZIP1 has “run” to its next target in the genome.

Figure 2

Transient “Hit‐and‐Run” targets of bZIP1 detected specifically in root cells are early responders that mediate bZIP1 downstream responses in planta. Rapid and transient “Hit‐and‐Run” targets of bZIP1 detected in isolated root cells 7 include TFs such as specific members of LBD and WRKY families 7. These LBDs and WRKYs have been shown to mediate life‐time traits of plants such as total protein content, shoot branching patterns 36 and leaf senescence 37.