Yeast transcription factor Msn2 binds to G4 DNA

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• G-quadruplex (G4) DNA structures are found in gene promoter regions and can regulate transcription.
• Stress response elements (STREs) are key binding sites for transcription factors Msn2 and Msn4, crucial for yeast stress response.

Purpose of the Study:

• To investigate the role of G4 DNA in Saccharomyces cerevisiae promoter regions.
• To determine if Msn2 and Msn4 transcription factors interact with G4 DNA structures.
• To elucidate the contribution of G4 DNA to transcriptional regulation in yeast.

Main Methods:

• Identification of G4 motifs in yeast gene promoters, particularly those overlapping with STREs.
• Analysis of Msn2 binding affinity to G4 DNA using biophysical methods.
• Genome-wide analysis of Msn2 enrichment at G4 DNA loci under stress conditions.
• Transcriptional analysis of genes with G4/STRE promoters upon treatment with G4 ligands and in mutant strains (msn2Δ msn4Δ).

Main Results:

• 37 genes with G4 motifs in promoters were identified, with 20 overlapping STREs.
• Msn2 directly binds G4 DNA via its zinc-finger domain with comparable affinity to STRE.
• Msn2 localizes to G4 DNA sites during stress, and G4 ligands increase transcription of G4/STRE genes.
• Transcriptional changes are dependent on Msn2/Msn4 and the integrity of the G4 motif.

Conclusions:

• G4 DNA serves as an alternative binding site for Msn2, in addition to STRE.
• G4 DNA formation is a significant factor in the transcriptional regulation of yeast genes, particularly under stress conditions.