title: Bisquinolinium compounds induce quadruplex-specific transcriptome changes in HeLa S3 cell lines.
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.
authors.affiliation: Department of Chemistry and Konstanz Research School Chemical Biology (KoRS-CB), University of Konstanz, Universitätsstraße 10, Konstanz, Germany.
authors.forename: Rashi
authors.initials: R
authors.lastname: Halder
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Riou
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
authors.forename: Tancred
authors.initials: T
authors.lastname: Frickey
authors.forename: Jörg S
authors.initials: JS
authors.lastname: Hartig
mesh_terms: D054856:G-Quadruplexes / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects*
chemical_list: C502660:2,6-N,N'-methyl-quinolinio-3-yl-pyridine dicarboxamide; D011725:Pyridines; D011804:Quinolines