Dept. of Pharmaceutical and Pharmacological Sciences, University of Padova, v. Marzolo, 5, 35131 Padova, Italy.
Dept. of Pharmaceutical and Pharmacological Sciences, University of Padova, v. Marzolo, 5, 35131 Padova, Italy.
Biochim Biophys Acta Gen Subj. 2017 May;1861(5 Pt B):1399-1413. doi: 10.1016/j.bbagen.2016.12.024. Epub 2016 Dec 24.
G-rich sequences undergo unique structural equilibria to form G-quadruplexes (G4) both in vitro and in cell systems. Several pathologies emerged to be directly related to G4 occurrence at defined genomic portions. Additionally, G-rich sequences are significantly represented around transcription start sites (TSS) thus leading to the hypothesis of a gene regulatory function for G4. Thus, the tuning of G4 formation has been proposed as a new powerful tool to regulate gene expression to treat related pathologies. However, up-to date this approach did not provide any new really efficient treatment.
Here, we summarize the most recent advances on the correlation between the structural features of G4 in human promoters and the role these systems physiologically exert. In particular we focus on the effect of G4 localization among cell compartments and along the promoters in correlation with protein interaction networks and epigenetic state. Finally the intrinsic structural features of G4 at promoters are discussed to unveil the contribution of different G4 structural modules in this complex architecture.
It emerges that G4s play several roles in the intriguing and complex mechanism of gene expression, being able to produce opposite effects on the same target. This reflects the occurrence of a highly variegate network of several components working simultaneously.
The resulting picture is still fuzzy but some points of strength are definitely emerging, which prompts all of us to strengthen our efforts in view of a selective control of gene expression through G4 modulation. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.
富含 G 的序列在体外和细胞系统中都能经历独特的结构平衡，形成 G-四链体 (G4)。几种病理学被发现与特定基因组区域的 G4 发生直接相关。此外，富含 G 的序列在转录起始位点 (TSS) 周围有显著的代表性，因此导致了 G4 具有基因调控功能的假说。因此，调节 G4 形成被提出作为一种新的强大工具来调节基因表达，以治疗相关的病理学。然而，迄今为止，这种方法并没有提供任何真正有效的新治疗方法。
在这里，我们总结了最近在人类启动子中 G4 的结构特征与这些系统在生理上发挥的作用之间的相关性的最新进展。特别是，我们关注 G4 在细胞区室之间和沿着启动子的定位与蛋白质相互作用网络和表观遗传状态的相关性。最后，讨论了启动子上 G4 的内在结构特征，以揭示不同 G4 结构模块在这种复杂结构中的贡献。
G4 在基因表达的复杂机制中发挥了多种作用，能够对同一靶标产生相反的影响，这表明存在一个由多个同时工作的组件组成的高度多样化的网络。
虽然结果仍然模糊，但肯定出现了一些有力的观点，这促使我们所有人都加强努力，通过 G4 调节选择性地控制基因表达。本文是一个题为“G-四链体”的特刊的一部分，客座编辑为 Dr. Concetta Giancola 和 Dr. Daniela Montesarchio。
