Transcription Factor Dynamics: One Molecule at a Time

Annu Rev Cell Dev Biol. 2023 Oct 16:39:277-305. doi: 10.1146/annurev-cellbio-022823-013847. Epub 2023 Aug 4.

Abstract

Cells must tightly regulate their gene expression programs and yet rapidly respond to acute biochemical and biophysical cues within their environment. This information is transmitted to the nucleus through various signaling cascades, culminating in the activation or repression of target genes. Transcription factors (TFs) are key mediators of these signals, binding to specific regulatory elements within chromatin. While live-cell imaging has conclusively proven that TF-chromatin interactions are highly dynamic, how such transient interactions can have long-term impacts on developmental trajectories and disease progression is still largely unclear. In this review, we summarize our current understanding of the dynamic nature of TF functions, starting with a historical overview of early live-cell experiments. We highlight key factors that govern TF dynamics and how TF dynamics, in turn, affect downstream transcriptional bursting. Finally, we conclude with open challenges and emerging technologies that will further our understanding of transcriptional regulation.

Keywords: chromatin dynamics; gene regulation; genome organization; single-molecule tracking; transcription factor dynamics; transcriptional bursting.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromatin / genetics
  • Gene Expression Regulation*
  • Regulatory Sequences, Nucleic Acid
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism

Substances

  • Transcription Factors
  • Chromatin