Wu Wei-Sheng, Li Wen-Hsiung, Chen Bor-Sen
Lab of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu, 300, Taiwan.
Gene Regul Syst Bio. 2008 Feb 10;2:53-62. doi: 10.4137/grsb.s558.
Unicellular organisms such as yeasts have evolved mechanisms to respond to environmental stresses by rapidly reorganizing the gene expression program. Although many stress-response genes in yeast have been discovered by DNA microarrays, the stress-response transcription factors (TFs) that regulate these stress-response genes remain to be investigated. In this study, we use a dynamic system model of gene regulation to describe the mechanism of how TFs may control a gene's expression. Then, based on the dynamic system model, we develop the Stress Regulator Identification Algorithm (SRIA) to identify stress-response TFs for six kinds of stresses. We identified some general stress-response TFs that respond to various stresses and some specific stress-response TFs that respond to one specific stress. The biological significance of our findings is validated by the literature. We found that a small number of TFs is probably sufficient to control a wide variety of expression patterns in yeast under different stresses. Two implications can be inferred from this observation. First, the response mechanisms to different stresses may have a bow-tie structure. Second, there may be regulatory cross-talks among different stress responses. In conclusion, this study proposes a network of stress-response regulators and the details of their actions.
诸如酵母之类的单细胞生物已经进化出通过快速重组基因表达程序来应对环境压力的机制。尽管通过DNA微阵列已经发现了酵母中的许多应激反应基因，但调节这些应激反应基因的应激反应转录因子（TFs）仍有待研究。在本研究中，我们使用基因调控的动态系统模型来描述TFs可能如何控制基因表达的机制。然后，基于该动态系统模型，我们开发了应激调节因子识别算法（SRIA）来识别六种应激的应激反应TFs。我们鉴定出了一些对各种应激有反应的一般应激反应TFs和一些对一种特定应激有反应的特定应激反应TFs。我们研究结果的生物学意义得到了文献的验证。我们发现，在不同应激条件下，少数TFs可能足以控制酵母中广泛的表达模式。从这一观察结果可以推断出两个结论。第一，对不同应激的反应机制可能具有蝴蝶结结构。第二不同应激反应之间可能存在调节性串扰。总之，本研究提出了一个应激反应调节因子网络及其作用细节。
