Abstract

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.

Highlights

  • DNA regulation is a complex process involving interactions among genomic, cellular, and environmental factors

  • DNA largely exists in the well-recognised helical form (B-DNA), nucleotide bases can potentially interact in a variety of orientations

  • During PCR amplification of a differentially methylated gene locus, we found that the combination of cytosine methylation and G4 formation can have profound effects on amplification efficiency, which leads to allelic drop-out of methylated DNA during PCR [86]

Read more

Summary

Introduction

DNA regulation is a complex process involving interactions among genomic, cellular, and environmental factors. The potential effect that cytosine methylation may have on promoting or hindering non B-DNA formations has remained largely un-researched, despite this being a potential mechanism through which epigenetic factors could regulate gene activity. Such interactions could represent novel mechanisms for important biological functions, such as the regulation of gene expression, altering nucleosome positioning (stable G4s induce subsequent genomic rearrangements), or the control of genomic imprinting

G4 Formation and Cytosine Methylation
Cytosine Methylation Stabilises Non Watson-Crick Base Pairs
Cytosine Methylation and G4 Formation in RNA
In Vitro Effects of G4 and DNA Methylation
Potential In Vivo Effects of G4 and Methylation
Potential for Novel G4 Formation in Cancer Due to Abnormal Methylation
Conclusions
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call