Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, DK-2100, Copenhagen, Denmark.
Simons Centre for the Study of Living Machines, National Centre for Biological Sciences-TIFR, GKVK Campus, Bellary Road, Bangalore, 560065, India.
Nat Commun. 2019 Jan 8;10(1):71. doi: 10.1038/s41467-018-07932-1.
The control of proteins by a transcription factor with periodically varying concentration exhibits intriguing dynamical behaviour. Even though it is accepted that transcription factors vary their dynamics in response to different situations, insight into how this affects downstream genes is lacking. Here, we investigate how oscillations and chaotic dynamics in the transcription factor NF-κB can affect downstream protein production. We describe how it is possible to control the effective dynamics of the transcription factor by stimulating it with an oscillating ligand. We find that chaotic dynamics modulates gene expression and up-regulates certain families of low-affinity genes, even in the presence of extrinsic and intrinsic noise. Furthermore, this leads to an increase in the production of protein complexes and the efficiency of their assembly. Finally, we show how chaotic dynamics creates a heterogeneous population of cell states, and describe how this can be beneficial in multi-toxic environments.
转录因子浓度的周期性变化对蛋白质的控制表现出有趣的动力学行为。尽管人们普遍认为转录因子会根据不同的情况改变其动力学，但对于这如何影响下游基因却缺乏了解。在这里，我们研究了 NF-κB 转录因子的振荡和混沌动力学如何影响下游蛋白质的产生。我们描述了如何通过用振荡配体刺激转录因子来控制其有效动力学。我们发现，即使存在外在和内在噪声，混沌动力学也可以调节基因表达并上调某些低亲和力基因家族。此外，这会导致蛋白质复合物的产量增加及其组装效率提高。最后，我们展示了混沌动力学如何产生细胞状态的异质群体，并描述了在多毒性环境中这如何有益。
