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通过G-四链体的参与深入了解在血流形式和前循环形式中基因表达的表观遗传调控。

Insight into the epigenetic regulation of gene expression in the bloodstream and procyclic forms of through the involvement of G-quadruplexes.

作者信息

Belmonte-Reche Efres, Martínez-García Marta, de Jong Anne, Kuipers Oscar P, Cebrián Rubén

机构信息

Centre for Genomics and Oncological Research (GENYO), Avenida de la Ilustración 114, 18016, Granada , Spain.

Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, 18071, Granada, Spain.

出版信息

NAR Genom Bioinform. 2025 Jul 17;7(3):lqaf100. doi: 10.1093/nargab/lqaf100. eCollection 2025 Sep.

DOI:10.1093/nargab/lqaf100
PMID:40677914
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12267983/
Abstract

This study explores how G-quadruplexes (G4s) influence gene expression during the transition between bloodstream (BF) and procyclic (PC) forms of . Computational analysis identified over 115 000 G4-prone sequences, with 63% predicted to form stable G4 structures. These sequences are enriched in regions associated with antigenic variation, suggesting a role in gene regulation. Experimental validation using G4 ligands (AQ1, Pt-TTPY, and pyridostatin) showed a consistent downregulation of differentially expressed genes, supporting the potential relevance of targeting G4s. These results contribute to our understanding of epigenetic regulation in and may help inform future approaches for managing parasitic infections.

摘要

本研究探讨了G-四链体（G4s）在布氏锥虫血流（BF）型和前循环（PC）型转变过程中如何影响基因表达。通过计算分析确定了超过115000个易于形成G4的序列，其中63%预计会形成稳定的G4结构。这些序列在与抗原变异相关的区域富集，表明其在基因调控中发挥作用。使用G4配体（AQ1、Pt-TTPY和吡啶氨菌素）进行的实验验证显示，差异表达基因持续下调，支持了靶向G4s的潜在相关性。这些结果有助于我们理解布氏锥虫的表观遗传调控，并可能为未来管理寄生虫感染的方法提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/b95a5d52932b/lqaf100fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/880830d148b0/lqaf100fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/e8404f2e1a13/lqaf100fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/7114de6ba023/lqaf100fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/7c03249a58df/lqaf100fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/16f592fa336f/lqaf100fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/b95a5d52932b/lqaf100fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/880830d148b0/lqaf100fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/e8404f2e1a13/lqaf100fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/7114de6ba023/lqaf100fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/7c03249a58df/lqaf100fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/16f592fa336f/lqaf100fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b3d/12267983/b95a5d52932b/lqaf100fig6.jpg

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G-Quadruplexes as Key Transcriptional Regulators in Neglected Trypanosomatid Parasites.G-四链体作为被忽视的动基体目寄生虫中转录调控的关键。
Chembiochem. 2023 Jun 15;24(12):e202300265. doi: 10.1002/cbic.202300265. Epub 2023 May 23.
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G-Quadruplex DNA as a Target in Pathogenic Bacteria: Efficacy of an Extended Naphthalene Diimide Ligand and Its Mode of Action.
G-四链体 DNA 作为致病细菌的靶点：扩展的萘二酰亚胺配体的功效及其作用模式。
J Med Chem. 2022 Mar 24;65(6):4752-4766. doi: 10.1021/acs.jmedchem.1c01905. Epub 2021 Dec 20.
4
G4LDB 2.2: a database for discovering and studying G-quadruplex and i-Motif ligands.G4LDB 2.2：一个用于发现和研究 G-四链体和 i-Motif 配体的数据库。
Nucleic Acids Res. 2022 Jan 7;50(D1):D150-D160. doi: 10.1093/nar/gkab952.
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G-quadruplex DNA: a novel target for drug design.G-四链体 DNA：药物设计的新靶标。
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