Meyer Kirstin, Huang Bo, Weiner Orion D
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA.
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Nat Rev Genet. 2025 Apr 16. doi: 10.1038/s41576-025-00837-y.
Transcription factors relay information from the external environment to gene regulatory networks that control cell physiology. To confer signalling specificity, robustness and coordination, these signalling networks use temporal communication codes, such as the amplitude, duration or frequency of signals. Although much is known about how temporal information is encoded, a mechanistic understanding of how gene regulatory networks decode signalling dynamics is lacking. Recent advances in our understanding of phase separation of transcriptional condensates provide new biophysical frameworks for both temporal encoding and decoding mechanisms. In this Perspective, we summarize the mechanisms by which transcriptional condensates could enable temporal decoding through signal adaptation, memory and persistence. We further outline methods to probe and manipulate dynamic communication codes of transcription factors and condensates to rationally control gene activation.
转录因子将来自外部环境的信息传递给控制细胞生理的基因调控网络。为了赋予信号特异性、稳健性和协调性,这些信号网络使用时间通信代码,如信号的幅度、持续时间或频率。尽管我们对时间信息的编码方式已经有了很多了解,但对于基因调控网络如何解码信号动态变化仍缺乏机制上的理解。我们对转录凝聚物相分离的最新认识进展为时间编码和解码机制提供了新的生物物理框架。在这篇观点文章中,我们总结了转录凝聚物通过信号适应、记忆和持续性实现时间解码的机制。我们还进一步概述了探测和操纵转录因子及凝聚物的动态通信代码以合理控制基因激活的方法。