Fig. 1: Factors affecting G4 structure formation and stability.

a Due to the unique negative charge channels in the G4 structure, it is stabilized upon interacting with cations such as K⁺, Na⁺, and Li⁺ through electrostatic forces. b Small molecules and ligands enhance G4 structural stability. c Helicase is involved in regulating the transcription and translation of genes by unwinding G4s. DNA helicases accelerate the unwinding of promoter region G4s and promote the transcription of genes by RNA polymerase (Pol II). RNA G4s are unstable and can be easily unwound by RNA helicases, thereby facilitating the translation process. d Interaction of DNA methylation and G4s: although CpG methylation can block the formation of G4 structures in the region harboring CpG islands, it can recruit TFs to the G4 motifs formed in hypomethylated regions, thereby promoting gene replication and transcription. In addition, the G4s can also reverse CpG methylation and maintain the hypomethylated state.