Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA; email:
Department of Physics, University of Maryland, College Park, Maryland, USA; email:
Annu Rev Cell Dev Biol. 2023 Oct 16;39:277-305. doi: 10.1146/annurev-cellbio-022823-013847. Epub 2023 Aug 4.
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.
细胞必须严格调控其基因表达程序，但又要能快速响应其环境中的急性生化和生物物理线索。这些信息通过各种信号级联传递到细胞核，最终导致靶基因的激活或抑制。转录因子（TFs）是这些信号的关键介质，它们与染色质中的特定调节元件结合。虽然活细胞成像已经确凿地证明了 TF-染色质相互作用具有高度动态性，但这种短暂的相互作用如何对发育轨迹和疾病进展产生长期影响，在很大程度上仍然不清楚。在这篇综述中，我们总结了我们对 TF 功能的动态性质的现有理解，从早期活细胞实验的历史概述开始。我们强调了控制 TF 动力学的关键因素，以及 TF 动力学如何反过来影响下游转录爆发。最后，我们以尚未解决的问题和新兴技术作为结束，这些问题和技术将进一步加深我们对转录调控的理解。
