Homotypic clusters of transcription factor binding sites: A model system for understanding the physical mechanics of gene expression.
Homotypic clusters of transcription factor binding sites: A model system for understanding the physical mechanics of gene expression.
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DOI：
10.1016/j.csbj.2014.07.005
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发表时间：
2014-07
影响因子：
6
通讯作者：
Adryan, Boris
中科院分区：
文献类型：
--
作者：
Ezer, Daphne;Zabet, Nicolae Radu;Adryan, Boris
顺式调节元件中结合位点的组织可以通过多种物理机制的组合来影响基因的表达，从TF分子之间的直接相互作用到DNA环和瞬时染色质相互作用。对启动子和其他CRE中简单和常见的构建块的研究使我们能够剖析所有这些机制是如何协同工作的。同一Tf物种的许多相邻的Tf结合位点形成同型簇，这些Cre结构构建块是理解相互作用转录机制的主要候选者。同型簇广泛存在于细菌和真核生物基因组中，存在于启动子和更远端的增强子/沉默元件中。在这里，我们回顾了以前的理论和实验研究，这些研究表明同型簇的复杂性(结合位点的数量)和空间组织(位点之间的距离和到转录起始点的总距离)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，这是一种可以影响基因表达的机制，但尚未得到充分的表征。我们建议对同型簇进行进一步的实验，这将有助于开发基因表达的机制模型。
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.