Department of Computational Science and Engineering, Nagoya University, Nagoya, Japan.
Biophys J. 2011 Jan 5;100(1):126-34. doi: 10.1016/j.bpj.2010.11.016.
Enhancer-promoter interactions in eukaryotic genomes are often controlled by sequence elements that block the actions of enhancers. Although the experimental evidence suggests that those sequence elements contribute to forming loops of chromatin, the molecular mechanism of how such looping affects the enhancer-blocking activity is still largely unknown. In this article, the roles of DNA looping in enhancer blocking are investigated by numerically simulating the DNA conformation of a prototypical model system of gene regulation. The simulated results show that the enhancer function is indeed blocked when the enhancer is looped out so that it is separated from the promoter, which explains experimental observations of gene expression in the model system. The local structural distortion of DNA caused by looping is important for blocking, so the ability of looping to block enhancers can be lost when the loop length is much larger than the persistence length of the chain.
真核基因组中的增强子-启动子相互作用通常受到序列元件的控制，这些序列元件可以阻止增强子的作用。尽管实验证据表明，这些序列元件有助于形成染色质环，但这种环如何影响增强子阻断活性的分子机制在很大程度上仍然未知。在本文中，通过数值模拟基因调控的典型模型系统中的 DNA 构象，研究了 DNA 环化在增强子阻断中的作用。模拟结果表明，当增强子环化使其与启动子分离时，增强子的功能确实被阻断，这解释了模型系统中基因表达的实验观察结果。环化引起的 DNA 局部结构扭曲对于阻断很重要，因此当环的长度远大于链的持久性长度时，环化阻止增强子的能力可能会丧失。
