Sneppen Kim, Dodd Ian B, Shearwin Keith E, Palmer Adam C, Schubert Rachel A, Callen Benjamin P, Egan J Barry
NORDITA, Nordic Institute for Theoretical Physics, Niels Bohr Institute, Blegdamsvej 17, DK-2100 Copenhagen, Denmark.
J Mol Biol. 2005 Feb 18;346(2):399-409. doi: 10.1016/j.jmb.2004.11.075. Epub 2004 Dec 23.
Interactions between RNA polymerases (RNAP) resulting from tandem or convergent arrangements of promoters can cause transcriptional interference, often with important consequences for gene expression. However, it is not known what factors determine the magnitude of interference and which mechanisms are likely to predominate in any situation. We therefore developed a mathematical model incorporating three mechanisms of transcriptional interference in bacteria: occlusion (in which passing RNAPs block access to the promoter), collisions between elongating RNAPs, and "sitting duck" interference (in which RNAP complexes waiting to fire at the promoter are removed by passing RNAP). The predictions of the model are in good agreement with a recent quantitative in vivo study of convergent promoters in E.coli. Our analysis predicts that strong occlusion requires the interfering promoter to be very strong. Collisions can also produce strong interference but only if the interfering promoter is very strong or if the convergent promoters are far apart (>200 bp). For moderate strength interfering promoters and short inter-promoter distances, strong interference is dependent on the sitting duck mechanism. Sitting duck interference is dependent on the relative strengths of the two promoters. However, it is also dependent on the "aspect ratio" (the relative rates of RNAP binding and firing) of the sensitive promoter, allowing promoters of equal strength to have very different sensitivities to transcriptional interference. The model provides a framework for using transcriptional interference to investigate various dynamic processes on DNA in vivo.
由串联或汇聚排列的启动子所导致的RNA聚合酶（RNAP）之间的相互作用会引发转录干扰，这通常对基因表达具有重要影响。然而，尚不清楚哪些因素决定干扰的程度，以及在任何情况下哪种机制可能占主导地位。因此，我们构建了一个数学模型，该模型纳入了细菌中转录干扰的三种机制：阻碍（即过往的RNAP阻断对启动子的访问）、延伸中的RNAP之间的碰撞以及“坐鸭”干扰（即等待在启动子处起始转录的RNAP复合物被过往的RNAP清除）。该模型的预测结果与最近一项对大肠杆菌中汇聚型启动子进行的定量体内研究结果高度吻合。我们的分析预测，强烈的阻碍需要干扰性启动子非常强大。碰撞也能产生强烈的干扰，但前提是干扰性启动子非常强大，或者汇聚型启动子相距很远（>200 bp）。对于中等强度的干扰性启动子和较短的启动子间距离，强烈的干扰依赖于“坐鸭”机制。“坐鸭”干扰取决于两个启动子的相对强度。然而，它还取决于敏感启动子的“长宽比”（RNAP结合和起始转录的相对速率），这使得强度相同的启动子对转录干扰的敏感度可能有很大差异。该模型为利用转录干扰来研究体内DNA上的各种动态过程提供了一个框架。
