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Bisquinolinium compounds induce quadruplex-specific transcriptome changes in HeLa S3 cell lines.

Rashi Halder¹, Jean-Francois Riou, Marie-Paule Teulade-Fichou

¹Department of Chemistry and Konstanz Research School Chemical Biology (KoRS-CB), University of Konstanz, Universitätsstraße 10, Konstanz, Germany.

BMC Research Notes

|March 15, 2012

Summary

This summary is machine-generated.

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Guanosine-rich sequences form G-quadruplex motifs near gene start sites, impacting transcription. Specific bisquinolinium compounds like PhenDC3 and 360A alter gene expression, particularly for G-quadruplex containing genes.

Area of Science:

Genomics
Molecular Biology
Transcriptomics

Background:

G-quadruplex (G4) motifs, formed by guanosine-rich sequences, are prevalent near human gene transcription start sites (TSS).
G4 motifs in promoter regions significantly influence gene transcription at the single-gene level.
Targeting promoter G4 motifs with small molecules can further modulate transcription levels.

Purpose of the Study:

To investigate the global effects of G-quadruplex-specific small molecules on the human transcriptome.
To assess the specificity of bisquinolinium derivatives PhenDC3 and 360A in modulating gene expression.

Main Methods:

Whole-transcriptome analysis of HeLa S3 cells treated with PhenDC3 and 360A.
Utilizing G-quadruplex-specific bisquinolinium derivatives (PhenDC3 and 360A).

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Confirmation of gene targeting specificity using real-time PCR.

Main Results:

Treatment with PhenDC3 and 360A induced widespread changes in the transcriptome.
These transcriptomic changes were specific to genes possessing G-quadruplex motifs near their TSS.
Real-time PCR confirmed PhenDC3 and 360A as potent modulators of G-quadruplex-regulated genes.

Conclusions:

Specific modulation of G-quadruplex-containing genes is achievable using whole-transcriptome analysis.
Quadruplex-selective bisquinolinium compounds effectively target and alter the expression of G4-motif-containing genes in cultured cells.