Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India.
PLoS One. 2012;7(7):e41027. doi: 10.1371/journal.pone.0041027. Epub 2012 Jul 20.
Feedforward loops (FFLs) consist of three genes which code for three different transcription factors A, B and C where B regulates C and A regulates both B and C. We develop a detailed model to describe the dynamical behavior of various types of coherent and incoherent FFLs in the transcription factor networks. We consider the deterministic and stochastic dynamics of both promoter-states and synthesis and degradation of mRNAs of various genes associated with FFL motifs. Detailed analysis shows that the response times of FFLs strongly dependent on the ratios (w(h) = γ(pc)/γ(ph) where h = a, b, c corresponding to genes A, B and C) between the lifetimes of mRNAs (1/γ(mh)) of genes A, B and C and the protein of C (1/γ(pc)). Under strong binding conditions we can categorize all the possible types of FFLs into groups I, II and III based on the dependence of the response times of FFLs on w(h). Group I that includes C1 and I1 type FFLs seem to be less sensitive to the changes in w(h). The coherent C1 type seems to be more robust against changes in other system parameters. We argue that this could be one of the reasons for the abundant nature of C1 type coherent FFLs.
前馈环（FFL）由三个基因组成，这三个基因编码三个不同的转录因子 A、B 和 C，其中 B 调节 C，A 调节 B 和 C。我们开发了一个详细的模型来描述转录因子网络中各种类型的相干和非相干 FFL 的动态行为。我们考虑了与 FFL 基序相关的各种基因的启动子状态和 mRNA 的合成和降解的确定性和随机动力学。详细分析表明，FFL 的响应时间强烈依赖于基因 A、B 和 C 的 mRNA（1/γ(mh)）的寿命（1/γ(mh)）与 C 蛋白（1/γ(pc)）之间的比值（w(h) = γ(pc)/γ(ph)，其中 h = a、b、c 分别对应于基因 A、B 和 C）。在强结合条件下，我们可以根据 FFL 的响应时间对 w(h)的依赖性将所有可能的 FFL 类型分为 I、II 和 III 组。包括 C1 和 I1 型 FFL 的组 I 似乎对 w(h)的变化不太敏感。相干的 C1 型似乎对其他系统参数的变化更具鲁棒性。我们认为这可能是 C1 型相干 FFL 大量存在的原因之一。
