Bisquinolinium compounds induce quadruplex-specific transcriptome changes in HeLa S3 cell lines
1 Department of Chemistry and Konstanz Research School Chemical Biology (KoRS-CB), University of Konstanz, Universitätsstraße 10, 78457 Konstanz, Germany
2 Structure des Acides Nucléiques, Télomères et Evolution, INSERM U565, CNRS UMR 7196, Muséum National d'Histoire Naturelle, 43 rue Cuvier, 75231 Paris cedex 05, France
3 Institut Curie, UMR 176-CNRS, Bât 110, Université Paris-Sud, 91405 Orsay, France
4 Department of Biology, University of Konstanz, Universitätsstraße 10, 78457 Konstanz, Germany
BMC Research Notes 2012, 5:138 doi:10.1186/1756-0500-5-138Published: 13 March 2012
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.
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.
Specific effects on quadruplex-containing genes have been observed utilizing whole-transcriptome analysis upon treatment of cultured cells with quadruplex-selective bisquinolinium compounds.