G-quadruplex structures as modulators of alternative promoter usage.

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.