Computational Systems Biology Research Group, Department of Signal Processing, Tampere University of Technology, Finland.
J Theor Biol. 2009 Dec 7;261(3):441-8. doi: 10.1016/j.jtbi.2009.08.024. Epub 2009 Aug 25.
We investigate how the regulation of protein multi-functionalities affect the dynamics of a stochastic model of a toggle switch and the differentiation pattern of cell population regulated by the switch. We study the effects of loss of functionality in DNA-binding and repression and the involvement in differentiation pathway choice. First is shown how the patterns of cell differentiation differ, when each of these functionalities is fully non-functional. Next, tuning the fraction of non-functional proteins regarding the ability to bind DNA is shown to allow fine tuning of the switch and cell differentiation pattern dynamics. Finally, biasing the probability of functionality of the two proteins biases the dynamics of the switch and cell differentiation patterns, especially when transcription factors retain the ability to bind DNA but have lost the ability to repress gene expression. Our results suggest that, besides transcriptional and translational levels of regulation, activation of functionalities in multi-functional proteins are an important regulator of gene networks.
我们研究了蛋白质多功能性的调节如何影响振子开关的随机模型的动力学以及由该开关调节的细胞群体的分化模式。我们研究了 DNA 结合和抑制功能丧失以及参与分化途径选择的影响。首先，当这些功能中的每一个完全无功能时，显示细胞分化的模式如何不同。接下来，调节与结合 DNA 的能力相关的无功能蛋白质的分数被显示为允许微调开关和细胞分化模式动力学。最后，偏向两个蛋白质的功能的概率会偏向开关和细胞分化模式的动力学，特别是当转录因子保留结合 DNA 的能力但失去抑制基因表达的能力时。我们的结果表明，除了转录和翻译水平的调节外，多功能蛋白质中功能的激活是基因网络的重要调节剂。
