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G-quadruplex structures as modulators of alternative promoter usage.

Rongxin Zhang^1,2, Jean-Louis Mergny¹

¹Laboratoire d'Optique et Biosciences (LOB), Ecole Polytechnique, CNRS, INSERM, Institut Polytechnique de Paris, Palaiseau 91120, France.

NAR Genomics and Bioinformatics

|January 2, 2026

Summary

G-quadruplexes (G4s) regulate gene expression by influencing alternative promoter (AP) selection. This study shows G4 structures promote AP usage, impacting transcript diversity in cancer cells.

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Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1

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Published on: May 27, 2016

Area of Science:

Molecular Biology
Genomics
Epigenetics

Background:

Gene transcription is precisely regulated by promoters, crucial for transcript diversity.
Mechanisms governing promoter selection remain incompletely understood.
G-quadruplexes (G4s) are emerging as key regulators of gene expression.

Purpose of the Study:

To investigate the relationship between G4 structures and alternative promoters (APs).
To understand how G4s influence AP selection and transcript diversity.

Main Methods:

Systematic analysis integrating native elongating transcript-cap analysis of gene expression (NET-seq) and G4 ChIP-seq.
Studied K562 and HepG2 cancer cell lines.
Investigated the effect of G4 ligands on AP generation.

Main Results:

Identified 573 differentially utilized APs.
26% of APs were associated with G4 structures within 100 base pairs.
G4-associated promoters showed predominantly increased activity, suggesting G4s promote AP selection.
G4 ligand treatment induced AP generation, indicating G4 stabilization modulates AP usage.

Conclusions:

G4 structures play a significant role in regulating alternative promoter usage.
G4s generally promote the selection of alternative promoters, contributing to transcript isoform diversity.
Findings offer novel insights into G4-mediated regulation of gene expression and transcript diversity.