Murugan Rajamanickam
Department of Chemistry and Biochemistry, Center for Biomolecular Structure and Organization, University of Maryland, College Park, MD 20742, USA.
J Theor Biol. 2007 Oct 21;248(4):696-705. doi: 10.1016/j.jtbi.2007.06.003. Epub 2007 Jun 9.
Enhancers are important regulatory elements associated with eukaryotic genes. Here we present a random jump model on enhancer action at distance along the DNA. We show that to initiate the enhancing-action of an enhancer, a minimum jump size k=k(omega) which is directly proportional to the size of the genome, must be possessed by the RNA polymerase (RNAP) in the process of searching for the promoter sequences. When the jump size is near to or above k(omega), our model predicts that enhancers increase the level of expression of a gene mainly by increasing the probability of the gene to get transcribed rather than by increasing the transcriptional rate. Apart from this, our model also predicts that enhancer can increase the transcriptional probability only in the presence of the memory of the first time enhancer-RNAP contact. When the jump size associated with dynamics of RNAP on the DNA is close to or above certain critical values k=k(c) approximately 2N(2/3)where N is the length of the DNA under consideration, enhancers can regulate the transcription of a gene in a position and distance independent manner and at the jump size k=k(c) the enhancing action is a maximum. Since the jump size k is directly proportional to the degree of super-coiling or close-packed nature the DNA, our model suggests that to initiate the enhancer action a minimum degree of super-coiling of DNA is necessary that corresponds to the requirement of a minimum jump size k=k(omega) which agrees well with the experimental observations.
增强子是与真核基因相关的重要调控元件。在此,我们提出了一种关于增强子沿DNA远距离作用的随机跳跃模型。我们表明,为了启动增强子的增强作用,RNA聚合酶(RNAP)在搜索启动子序列的过程中必须具备一个与基因组大小直接成正比的最小跳跃大小k = k(ω)。当跳跃大小接近或高于k(ω)时,我们的模型预测增强子主要通过增加基因被转录的概率而非提高转录速率来增加基因的表达水平。除此之外,我们的模型还预测增强子只有在存在首次增强子 - RNAP接触记忆的情况下才能增加转录概率。当与RNAP在DNA上的动态相关的跳跃大小接近或高于某个临界值k = k(c) ≈ 2N(2/3)(其中N是所考虑的DNA长度)时,增强子可以以位置和距离无关的方式调节基因转录,并且在跳跃大小k = k(c)时增强作用最大。由于跳跃大小k与DNA的超螺旋程度或紧密堆积性质直接成正比,我们的模型表明启动增强子作用需要DNA有一个最小超螺旋程度,这与最小跳跃大小k = k(ω)的要求相对应,这与实验观察结果非常吻合。