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

Halder R, Riou JF, Teulade-Fichou MP, Frickey T, Hartig JS - BMC Res Notes (2012)

Bottom Line: 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).Specific effects on quadruplex-containing genes have been observed utilizing whole-transcriptome analysis upon treatment of cultured cells with quadruplex-selective bisquinolinium compounds.

View Article: PubMed Central - HTML - PubMed

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

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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Distribution of G-quadruplex motifs with respect to TSS (before or after) and DNA strand (forward or reverse) in af(after-forward), ar(after-reverse), bf (before-forward) and br (before-reverse) subsets.
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Figure 4: Distribution of G-quadruplex motifs with respect to TSS (before or after) and DNA strand (forward or reverse) in af(after-forward), ar(after-reverse), bf (before-forward) and br (before-reverse) subsets.

Mentions: To investigate the effect of the position of G-quadruplexes with respect to the TSS and strand orientation, we further compared the number of G-quadruplexes in the up- and down-regulated genes with the set of genes showing no significant change in expression that also harbored quadruplexes in their ± 2 kb region (non-differentially expressed genes common between all the gene sets, anova > 0.75). These were divided into 4 subsets each: 1) af: G4-motifs present after TSS on forward strand, 2) ar: after TSS on reverse strand, 3) bf: before TSS on forward strand and 4) br: before TSS on reverse strand (Additional file 1: Table S1). Interestingly, we found that the number of G-quadruplexes in category af and br are significantly higher for the up- and down-regulated genes (both examined molecules) than unchanged/non-differentially expressed genes and have lower representation for category bf (hypergeometric test, p < 0.05, Figure 4).


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

Halder R, Riou JF, Teulade-Fichou MP, Frickey T, Hartig JS - BMC Res Notes (2012)

Distribution of G-quadruplex motifs with respect to TSS (before or after) and DNA strand (forward or reverse) in af(after-forward), ar(after-reverse), bf (before-forward) and br (before-reverse) subsets.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3375199&req=5

Figure 4: Distribution of G-quadruplex motifs with respect to TSS (before or after) and DNA strand (forward or reverse) in af(after-forward), ar(after-reverse), bf (before-forward) and br (before-reverse) subsets.
Mentions: To investigate the effect of the position of G-quadruplexes with respect to the TSS and strand orientation, we further compared the number of G-quadruplexes in the up- and down-regulated genes with the set of genes showing no significant change in expression that also harbored quadruplexes in their ± 2 kb region (non-differentially expressed genes common between all the gene sets, anova > 0.75). These were divided into 4 subsets each: 1) af: G4-motifs present after TSS on forward strand, 2) ar: after TSS on reverse strand, 3) bf: before TSS on forward strand and 4) br: before TSS on reverse strand (Additional file 1: Table S1). Interestingly, we found that the number of G-quadruplexes in category af and br are significantly higher for the up- and down-regulated genes (both examined molecules) than unchanged/non-differentially expressed genes and have lower representation for category bf (hypergeometric test, p < 0.05, Figure 4).

Bottom Line: 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).Specific effects on quadruplex-containing genes have been observed utilizing whole-transcriptome analysis upon treatment of cultured cells with quadruplex-selective bisquinolinium compounds.

View Article: PubMed Central - HTML - PubMed

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

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.

Show MeSH