Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.
Phys Biol. 2012 Aug;9(4):045007. doi: 10.1088/1478-3975/9/4/045007. Epub 2012 Aug 7.
Gene expression is frequently regulated by multiple transcription factors (TFs). Thermostatistical methods allow for a quantitative description of interactions between TFs, RNA polymerase and DNA, and their impact on the transcription rates. We illustrate three different scales of the thermostatistical approach: the microscale of TF molecules, the mesoscale of promoter energy levels and the macroscale of transcriptionally active and inactive cells in a cell population. We demonstrate versatility of combinatorial transcriptional activation by exemplifying logic functions, such as AND and OR gates. We discuss a metric for cell-to-cell transcriptional activation variability known as Fermi entropy. Suitability of thermostatistical modeling is illustrated by describing the experimental data on transcriptional induction of NFκB and the c-Fos protein.
基因表达通常受到多个转录因子(TFs)的调控。统计热力学方法允许对 TF、RNA 聚合酶和 DNA 之间的相互作用进行定量描述,以及它们对转录速率的影响。我们说明了统计热力学方法的三个不同尺度:TF 分子的微观尺度、启动子能级的中观尺度和细胞群体中转录活跃和不活跃细胞的宏观尺度。我们通过举例说明逻辑功能(如 AND 和 OR 门)来展示组合转录激活的多功能性。我们讨论了一种称为费米熵的细胞间转录激活可变性度量。通过描述 NFκB 和 c-Fos 蛋白转录诱导的实验数据,说明了统计热力学建模的适用性。