Beyond Structure: Methylation Fine-Tunes Stability and Folding Kinetics of bcl2Mid G-Quadruplex.

ABSTRACT: Cytosine methylation, a key epigenetic modification in the regulation of gene expression, raises intriguing questions about its role in the formation and thermodynamic stability of G-quadruplex (G4) structures. We investigated the impact of the 5-methylcytosine residue (C^m) on the well-characterized bcl2Mid G4 structure that forms in a GC-rich region of the B-cell lymphoma 2 (BCL2) gene promoter, which influences its expression. Using solution-state NMR and biophysical techniques, we discovered an unexpected sequence-specific effect of C^m on the folding kinetics of bcl2Mid G4. Specifically, substituting cytosine at position C6 with C6^m  slows down G4 folding kinetics and influences the equilibrium between major and minor structures in the presence of K

SUBMITTER: Medved N 

PROVIDER: S-EPMC12144886 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature