Faculdade de Ciências e Tecnologia Universidade Nova de Lisboa, Monte da Caparica, 2829-516 Caparica, Portugal.
J Theor Biol. 2012 May 21;301:83-94. doi: 10.1016/j.jtbi.2012.02.015. Epub 2012 Feb 20.
Many pairs of genes in Escherichia coli are driven by closely spaced promoters. We study the dynamics of expression of such pairs of genes driven by a model at the molecule and nucleotide level with delayed stochastic dynamics as a function of the binding affinity of the RNA polymerase to the promoter region, of the geometry of the promoter, of the distance between transcription start sites (TSSs) and of the repression mechanism. We find that the rate limiting steps of transcription at the TSS, the closed and open complex formations, strongly affect the kinetics of RNA production for all promoter configurations. Beyond a certain rate of transcription initiation events, we find that the interference between polymerases correlates the dynamics of production of the two RNA molecules from the two TSS and affects the distribution of intervals between consecutive productions of RNA molecules. The degree of correlation depends on the geometry, the distance between TSSs and repressors. Small changes in the distance between TSSs can cause abrupt changes in behavior patterns, suggesting that the sequence between adjacent promoters may be subject to strong selective pressure. The results provide better understanding on the sequence level mechanisms of transcription regulation in bacteria and may aid in the genetic engineering of artificial circuits based on closely spaced promoters.
许多对大肠杆菌中的基因由紧密间隔的启动子驱动。我们研究了在分子和核苷酸水平上由模型驱动的这样的基因对的表达动力学，作为 RNA 聚合酶与启动子区域的结合亲和力、启动子的几何形状、转录起始位点 (TSS) 之间的距离和抑制机制的函数。我们发现，TSS 处转录的限速步骤，即封闭和开放复合物的形成，强烈影响所有启动子构型的 RNA 产生动力学。在一定的转录起始事件率之后，我们发现聚合酶之间的干扰与从两个 TSS 产生的两个 RNA 分子的动力学相关，并影响连续产生 RNA 分子之间的间隔分布。相关程度取决于几何形状、TSS 之间的距离和抑制剂。TSS 之间距离的微小变化会导致行为模式的突然变化，这表明相邻启动子之间的序列可能受到强烈的选择压力。这些结果提供了对细菌转录调控序列水平机制的更好理解，并可能有助于基于紧密间隔启动子的人工电路的基因工程。
