Ezer Daphne, Zabet Nicolae Radu, Adryan Boris
Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.
Comput Struct Biotechnol J. 2014 Aug 1;10(17):63-9. doi: 10.1016/j.csbj.2014.07.005. eCollection 2014 Jul.
The organization of binding sites in cis-regulatory elements (CREs) can influence gene expression through a combination of physical mechanisms, ranging from direct interactions between TF molecules to DNA looping and transient chromatin interactions. The study of simple and common building blocks in promoters and other CREs allows us to dissect how all of these mechanisms work together. Many adjacent TF binding sites for the same TF species form homotypic clusters, and these CRE architecture building blocks serve as a prime candidate for understanding interacting transcriptional mechanisms. Homotypic clusters are prevalent in both bacterial and eukaryotic genomes, and are present in both promoters as well as more distal enhancer/silencer elements. Here, we review previous theoretical and experimental studies that show how the complexity (number of binding sites) and spatial organization (distance between sites and overall distance from transcription start sites) of homotypic clusters influence gene expression. In particular, we describe how homotypic clusters modulate the temporal dynamics of TF binding, a mechanism that can affect gene expression, but which has not yet been sufficiently characterized. We propose further experiments on homotypic clusters that would be useful in developing mechanistic models of gene expression.
顺式调控元件（CREs）中结合位点的组织可以通过多种物理机制影响基因表达，这些机制涵盖从转录因子（TF）分子之间的直接相互作用到DNA环化以及瞬时染色质相互作用。对启动子和其他CREs中简单且常见的构建模块进行研究，有助于我们剖析所有这些机制是如何协同发挥作用的。同一TF种类的许多相邻TF结合位点形成同型簇，这些CRE结构构建模块是理解相互作用转录机制的主要候选对象。同型簇在细菌和真核生物基因组中都很普遍，在启动子以及更远端的增强子/沉默子元件中均有存在。在此，我们回顾先前的理论和实验研究，这些研究展示了同型簇的复杂性（结合位点数量）和空间组织（位点之间的距离以及与转录起始位点的总体距离）如何影响基因表达。特别是，我们描述了同型簇如何调节TF结合的时间动态，这是一种能够影响基因表达但尚未得到充分表征的机制。我们提出了关于同型簇的进一步实验，这些实验将有助于建立基因表达的机制模型。
