基因组G-四链体在转录调控中的作用机制研究进展
收稿日期: 2025-02-24
修回日期: 2025-04-08
网络出版日期: 2025-06-03
基金资助
国家自然科学基金面上项目(32370653)
Advances in functional mechanisms of genomic G-quadruplex structures in transcriptional regulation
Received date: 2025-02-24
Revised date: 2025-04-08
Online published: 2025-06-03
Supported by
National Natural Science Foundation of China(32370653)
G-四链体(G-quadruplex，G4)作为基因组中典型的非B型核酸二级结构，通过其独特的四链折叠构象广泛参与端粒稳态维持、DNA复制调控、基因转录及翻译调控等关键生物学过程。在哺乳动物基因组中，G4在功能调控区域的显著富集特征揭示了其在转录调控中具有关键作用。本文聚焦基因组内源G4的动态形成机制与转录调控功能，系统阐述了其通过三重分子路径调控基因表达：(1)介导转录激活复合物的空间组装；(2)动态调控组蛋白修饰和DNA甲基化等表观遗传事件；(3)重构三维染色质构象以建立转录活性微环境。通过整合G4拓扑表征技术及动态平衡网络的最新进展，本文明确了G4作为关键顺式调控元件的功能定位，并为靶向G4的治疗策略开发指明了方向。
贺珍珍, 陈晓峰, 侯越, 杨铁林, 杨波, 郭燕 . 基因组G-四链体在转录调控中的作用机制研究进展[J]. 遗传, 2025 , 47(12) : 1287 -1299 . DOI: 10.16288/j.yczz.25-055
As a canonical non-B DNA secondary structure, the G-quadruplex (G4) dynamically regulates core biological processes, including telomere homeostasis, DNA replication and gene transcription/translation—through its unique four-stranded conformation. The significant enrichment of G4 structures in regulatory regions, particularly promoter regions within mammalian genomes reveals their critical role in transcriptional regulation. In this review, we focus on the dynamic formation mechanisms and transcriptional regulatory functions of endogenous G4 structures, systematically elucidating their three molecular pathways in modulating gene expression: (1) orchestrating spatial assembly of transcription activation complexes; (2) dynamically regulating epigenetic modifications, includinghistone alterations and DNA methylation; (3) remodeling three-dimensional chromatin architecture to establish transcriptionally active microenvironments. By integrating advancements in G4 topological characterization techniques and dynamic equilibrium networks, this work highlights the role of the G4 as a critical cis-regulatory element and provides a theoretical framework for developing G4-targeted therapeutic strategies.
Key words： G-quadruplex (G4); transcription; epigenetics; 3D chromatin
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