基因组G-四链体在转录调控中的作用机制研究进展

doi:10.16288/j.yczz.25-055

遗传 ›› 2025, Vol. 47 ›› Issue (12): 1287-1299.doi: 10.16288/j.yczz.25-055

基因组G-四链体在转录调控中的作用机制研究进展

贺珍珍¹^,²(), 陈晓峰², 侯越², 杨铁林², 杨波¹(), 郭燕²()

1.陕西省人民医院骨科，西安交通大学第三附属医院，西安 710069
2.西安交通大学生命科学与技术学院，生物医学信息工程教育部重点实验室，西安 710049

收稿日期:2025-02-24 修回日期:2025-04-08 出版日期:2025-12-20 发布日期:2025-06-03
通讯作者: 杨波，博士，副主任医师，研究方向：疾病分子机制。E-mail: yangbo1981911@126.com;
作者简介:贺珍珍，硕士研究生，专业方向：分子遗传学。E-mail: hezz1121@stu.xjtu.edu.cn
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

Zhenzhen He¹^,²(), Xiaofeng Chen², Yue Hou², Tie-Lin Yang², Bo Yang¹(), Yan Guo²()

1. Department of Orthopaedics, Shaanxi Provincial People’s Hospital, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710069, China
2. Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China

Received:2025-02-24 Revised:2025-04-08 Published:2025-12-20 Online:2025-06-03
Supported by:
National Natural Science Foundation of China(32370653)

摘要/Abstract

摘要：

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。

关键词: G-四链体(G4), 转录, 表观遗传, 三维染色质

Abstract:

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

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.

Zhenzhen He, Xiaofeng Chen, Yue Hou, Tie-Lin Yang, Bo Yang, Yan Guo. Advances in functional mechanisms of genomic G-quadruplex structures in transcriptional regulation[J]. Hereditas(Beijing), 2025, 47(12): 1287-1299.

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检测对象	技术	优点	限制	应用举例
体外DNA序列	生物物理方法	能够依据热稳定性、紫外吸收峰等物理性质确定未知序列在体外能否折叠成G4并确定其构象	检测通量低，只能在体外检测	圆二色光谱^[21]、紫外熔融^[22]
体外DNA序列	生物化学方法	以单核苷酸分辨率确定长链DNA序列中G4的位置	具有细胞毒性，活性受限于溶剂可及性和局部离子环境	DMS foot printing^[16]
全基因组	计算预测	根据给定的核酸基序可以预测基因组潜在的G4形成序列	预测仅限于基因组序列，无法纳入三维分子间G4及排除因染色质结构无法形成的G4	QGRS mapper^[23]、G4 Hunter^[24]
	聚合酶链终止法结合二代测序	结合二代测序可以全面检测细胞中潜在G4，获得基因组G4图谱	使用提取后的DNA序列进行实验，检测结果不能代表细胞生理状态下的G4图谱	G4-seq^[15]
	依赖G4抗体的染色质免疫共沉淀	使用特异性抗体与固定后染色质(G4 ChIP-seq)或天然细胞(G4 CUT & Tag)中G4互作检测全基因组范围存在的G4，可用于研究细胞因素对G4形成动态的影响	需要ChIP级别的抗体，该法会受到批次效应影响，影响可重复性。	BG4 ChIP-seq^[17]、 BG4 CUT&Tag^[18]
活细胞G4动态表征	荧光稳定小分子配体	允许在活细胞中观察单个G4的动态形成，不影响G4折叠动力学	荧光配体对细胞环境中pH、离子环境的变化以及光照敏感，可能会影响荧光的持续观测	SiR-PyPDS^[25]

基因组G-四链体在转录调控中的作用机制研究进展

Advances in functional mechanisms of genomic G-quadruplex structures in transcriptional regulation

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