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

Abstract : ABSTRACT: BACKGROUND: Guanosine rich sequences capable of forming G-quadruplex (G4) motifs are enriched near the gene transcription start site (TSS) in the human genome. When probed at the single gene level, G-quadruplex motifs residing in promoter regions show substantial effects on gene transcription. Moreover, further changes in transcription levels are noticed when G4-motifs are targeted with G-quadruplex-specific small molecules. RESULTS: Global studies concerning general changes of the transcriptome via targeting promoter-based G-quadruplex motifs are very limited and have so far only been carried out with compounds displaying weak selectivity for quadruplex sequences. Here we utilize two G-quadruplex-specific bisquinolinium derivatives PhenDC3 and 360A and investigate their effects on the expression of the HeLa S3 transcriptome. Our results show wide-spread changes in the transcriptome with specificity for genes with G-quadruplex motifs near their transcription start sites (TSS). Using real-time PCR we further confirmed the specificity of PhenDC3 and 360A as potent molecules to target G-quadruplex-regulated genes. CONCLUSIONS: Specific effects on quadruplex-containing genes have been observed utilizing whole-transcriptome analysis upon treatment of cultured cells with quadruplex-selective bisquinolinium compounds.
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Submitted on : Thursday, June 14, 2012 - 5:09:10 PM
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Rashi Halder, Jean-Francois Riou, Marie-Paule Teulade-Fichou, Tancred Frickey, Jörg Hartig. Bisquinolinium compounds induce quadruplex-specific transcriptome changes in HeLa S3 cell lines.. BMC Research Notes, BioMed Central, 2012, 5 (1), pp.138. ⟨10.1186/1756-0500-5-138⟩. ⟨inserm-00708330⟩



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