Yeast transcription factor Msn2 binds to G4 DNA

Sequences capable of forming quadruplex or G4 DNA are prevalent in the promoter regions. The transformation from canonical to non-canonical secondary structure apparently regulates transcription of a number of human genes. In the budding yeast Saccharomyces cerevisiae, we identified 37 genes with a G4 motif in the promoters including 20 genes that contain stress response element (STRE) overlapping a G4 motif. STRE is the binding site of stress response regulators Msn2 and Msn4, transcription factors belonging to the C2H2 zinc-finger protein family. We show here that Msn2 binds directly to the G4 DNA structure through its zinc-finger domain with a dissociation constant similar to that of STRE-binding and that, in a stress condition, Msn2 is enriched at G4 DNA-forming loci in the yeast genome. For a large fraction of genes with G4/STRE-containing promoters, treating with G4-ligands led to significant elevations in transcription levels. Such transcriptional elevation was greatly diminished in a msn2 & UDelta; msn4 & UDelta; background and was partly muted when the G4 motif was disrupted. Taken together, our data suggest that G4 DNA could be an alternative binding site of Msn2 in addition to STRE, and that G4 DNA formation could be an important element of transcriptional regulation in yeast.

Automated summary

Sequences capable of forming quadruplex or G4 DNA are common in promoter regions and they regulate transcription of human genes by changing secondary structure. In the yeast Saccharomyces cerevisiae, we found 37 genes with a G4 motif in the promoters, including 20 genes with both G4 motif and stress response element (STRE). The transcription factor Msn2 directly binds to G4 DNA and is enriched at G4 DNA-forming loci in yeast genome. Treating with G4-ligands significantly increases transcription levels for most genes with G4/STRE-containing promoters, but this effect is diminished when msn2 & msn4 genes are deleted or when the G4 motif is disrupted.