The SNAIL1 promoter contains G-quadruplex structures regulating its gene expression and DNA replication

Area of Science:

• Molecular Biology
• Genetics
• Cancer Research

Background:

• SNAIL1 is crucial for epithelial-mesenchymal transition (EMT) and linked to cancer progression.
• Targeting SNAIL1 directly remains challenging, with limited knowledge on its regulation.

Purpose of the Study:

• Investigate the role of G-quadruplex structures in regulating SNAIL1 gene expression.
• Explore G-quadruplexes as potential therapeutic targets for cancer.

Main Methods:

• Circular dichroism, native PAGE, gel-shift assays, immunofluorescence, DMS footprinting, ChIP.
• Reporter assays to assess promoter activity.
• DNA synthesis studies to evaluate replication effects.

Main Results:

• Identified a G-quadruplex forming region in the SNAIL1 promoter.
• Demonstrated that G-quadruplex disruption enhances SNAIL1 transcription.
• Observed G-quadruplex-mediated replication retardation in the SNAIL1 promoter.
• Found enrichment of mutations in the G-quadruplex region of the SNAIL1 promoter in cancer cells.

Conclusions:

• G-quadruplex structures negatively regulate SNAIL1 expression.
• These structures play a role in SNAIL1 promoter replication.
• The G-quadruplex region's mutations highlight clinical relevance for altered SNAIL1 expression in cancer.