Destabilisation of the c-kit1 G-quadruplex structure by N-methyladenosine modification.

N-methyladenine (mdA) has been recently discovered in eukaryotic genomic DNA. However, there have been few reports on its biological roles. G-quadruplex (G4) is a non-canonical nucleic acid structure formed by the stacking of G-tetrads. G4-forming sequences are enriched with cis-regulatory elements in genomic DNA and the G4 structures have important roles in various cellular functions. We previously reported that CpG methylation stabilized vascular endothelial growth factor (VEGF) G4 structure. Here we report that mdA modification destabilizes the human c-kit1 G4 structure. These results suggest that epigenetic modifications may affect G4 formation in order to regulate the biological functions.