The Dynamic Regulation of G-Quadruplex DNA Structures by Cytosine Methylation

It is well known that certain non B-DNA structures, including G-quadruplexes, are key elements that can regulate gene expression. Here, we explore the theory that DNA modifications, such as methylation of cytosine, could act as a dynamic switch by promoting or alleviating the structural formation of G-quadruplex structures in DNA or RNA. The interaction between epigenetic DNA modifications, G4 formation, and the 3D architecture of the genome is a complex and developing area of research. Although there is growing evidence for such interactions, a great deal still remains to be discovered. In vivo, the potential effect that cytosine methylation may have on the formation of DNA structures has remained largely unresearched, despite this being a potential mechanism through which epigenetic factors could regulate gene activity. Such interactions could represent novel mechanisms for important biological functions, including altering nucleosome positioning or regulation of gene expression. Furthermore, promotion of strand-specific G-quadruplex formation in differentially methylated genes could have a dynamic role in directing X-inactivation or the control of imprinting, and would be a worthwhile focus for future research.