External Seminar "G-quadruplexes are nucleosome exclusion modules supporting constitutive promoter and enhancer activities" by Jean-Christophe Andrau

Abstract : G-quadruplexes (G4s) are stable single-stranded secondary DNA structures, alternative to Watson-Crick pairing in vitro and in vivo. Increasing evidences indicate their importance in nuclear processes such as replication, insulation and telomere structure and maintenance. Our group is interested in G4’s relation to transcription at both promoters and enhancers in which they are overrepresented. In mammals up to 80% of the promoters and 20% of the enhancers carry experimentally validated G4s, using various detection methods including G4access, a method we recently developed (1). We propose that G4s and G4 clusters function as nucleosome exclusion modules at both promoters and enhancers, in which they tend to promote a constitutive activity as opposed to more activable sequences. At promoters, we have shown G4s contribute to promoter proximal pause release (2) while at enhancers, they associate to the most active sequences. At model promoters and enhancers, mutating G4 potential abolished or decreased transcription, indicating their importance in sustaining activity, most likely through chromatin opening. Intriguingly, analysis of high-resolution long-distance interactions revealed that G4 enhancers cluster with each other as well as with promoters and as opposed to other enhancers. Finally, we have observed that in the primate neural lineage, G4s tend to appear at novel and active enhancers, suggesting that are under a positive selective pressure at least in this evolutionary branch.