2. Academic Validation
  3. Unveiling the role of G-quadruplex structure in promoter region: Regulation of ABCA1 expression in macrophages possibly via NONO protein recruitment

Unveiling the role of G-quadruplex structure in promoter region: Regulation of ABCA1 expression in macrophages possibly via NONO protein recruitment

  • Int J Biol Macromol. 2023 Jun 21;125443. doi: 10.1016/j.ijbiomac.2023.125443.
Chao-Da Xiao 1,  Meng-Hao Jia 2,  Ming-Qing Zhong 3,  Yan Xu 4,  Zu-Tao Yu 5,  Zhi-Yong He 3,  Xu Lu 3,  Yan Zhang 6,  Xue Zhou 3,  Lin-Yun Fu 3,  Xiang-Chun Shen 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China. Electronic address: xcd@gmc.edu.cn.
  • 2 State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China. Electronic address: jmh@stu.gmc.edu.cn.
  • 3 State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China.
  • 4 Division of Chemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
  • 5 Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
  • 6 Department of Radiology, Affiliated Hospital of Guizhou Medical University, Guiyang 550001, China.
  • 7 State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guiyang 550025, China. Electronic address: sxc@gmc.edu.cn.
PMID: 37353131 DOI: 10.1016/j.ijbiomac.2023.125443
Abstract

ABCA1 has been found to be critical for Cholesterol efflux in macrophages. Understanding the mechanism regulating ABCA1 expression is important for the prevention and treatment of atherosclerosis. In the present study, a G-quadruplex (G4) structure was identified in the ABCA1 promoter region. This G4 was shown to be essential for ABCA1 transcription. Stabilizing the G4 by ligands surprisingly upregulated ABCA1 expression in macrophages. Knocking out the G4 remarkably reduced ABCA1 expression, and abolished the increase of ABCA1 expression induced by the G4 ligand. By pull-down assays, the protein NONO was identified as an ABCA1 G4 binder. Overexpression or repression of NONO significantly induced upregulation and downregulation of ABCA1 expression, respectively. ChIP and EMSA experiments showed that the G4 ligand promoted the binding between the ABCA1 G4 and NONO, which led to more recruitment of NONO to the promoter region and enhanced ABCA1 transcription. Finally, the G4 ligand was shown to significantly reduce the accumulation of Cholesterol in macrophages. This study showed a new insight into the regulation of gene expression by G4, and provided a new molecular mechanism regulating ABCA1 expression in macrophages. Furthermore, the study showed a possible novel application of the G4 ligand: preventing and treating atherosclerosis.

Keywords

ABCA1; G-quadruplexes; Macrophages.

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