Zamora-Chimal C G, Zeron E S
Centro de Investigación y de Estudios Avanzados del IPN, Unidad Monterrey, Parque de Investigación e Innovación Tecnológica, Apodaca NL, México.
Centro de Investigación y de Estudios Avanzados del IPN, Departamento de Matemáticas, Av. Instituto Politécnico Nacional México DF, México.
In Silico Biol. 2015;12(1-2):69-82. doi: 10.3233/ISB-150465.
We develop an exact and flexible mathematical model for Lutz and Bujard's controllable promoters. It can be used as a building block for modeling genetic systems based on them. Special attention is paid to deduce all the model parameters from reported (in vitro) experimental data. We validate our model by comparing the regulatory ranges measured in vivo by Lutz and Bujard against the ranges predicted by the model, and which are calculated as the reporter activity obtained under inducing conditions divided by the activity measured under maximal repression. In particular, we verify Bond et al. assertion that the cooperativity between two lac operators can be assumed to be negligible when their central base pairs are separated by 22 or 32 bp [Gene repression by minimal lac loops in vivo, Nucleic Acids Res, 38 (2010) 8072-8082]. Moreover, we also find that the probability that two repressors LacI bind to these operators at the same time can be assumed to be negligible as well. We finally use the model for the promoter P(LlacO-1) to analyze a synthetic genetic oscillator recently build by Stricker et al. [A fast, robust and tunable synthetic gene oscillator, Nature, 456 (2008) 516-519].
我们为卢茨和布亚德的可控启动子开发了一个精确且灵活的数学模型。它可作为基于这些启动子构建遗传系统模型的一个构建模块。我们特别关注从已报道的（体外）实验数据中推导所有模型参数。我们通过将卢茨和布亚德在体内测量的调控范围与模型预测的范围进行比较来验证我们的模型，模型预测范围的计算方式是诱导条件下获得的报告基因活性除以最大抑制条件下测量的活性。特别是，我们验证了邦德等人的断言：当两个乳糖操纵子的中心碱基对相隔22或32个碱基对时，可假定它们之间的协同作用可忽略不计[《体内最小乳糖环介导的基因抑制》，《核酸研究》，38 (2010) 8072 - 8082]。此外，我们还发现两个阻遏蛋白LacI同时结合到这些操纵子上的概率也可假定为可忽略不计。我们最终使用该启动子P(LlacO - 1)的模型来分析斯特里克等人最近构建的一个合成基因振荡器[《一个快速、稳健且可调谐的合成基因振荡器》，《自然》，456 (2008) 516 - 519]。
