About event
The global rise in obesity and its association with metabolic diseases (MetDs) as well as their elevated cancer risk pose them a major health challenge. While the mechanisms driving MetD progression remain unclear, both genetic and environmental factors, including DNA methylation, play key roles. Emerging evidence suggests that deregulated DNA methylation and G-quadruplexes (G4s) contribute to the observed deregulated transcription patterns. To investigate their impact, we analyzed DNA methylation in 160 MetD patients versus controls, focusing on overlaps with G4 formation and alternative promoter usage.
Illumina MethylationEPICv2 arrays (~900,000 CpGs) identified significant differential methylation in regulatory regions enriched for predicted G4 motifs. These regions overlapped with differentially methylated sites and deregulated alternative promoters in cancer. Using permanganate/S1 nuclease footprinting with direct adapter ligation (PDAL-Seq) and circular dichroism spectroscopy, we confirmed G4 formation in hypomethylated regions and identified a transcription factor and epigenetic regulator associated with these sites. Targeted in vitro studies revealed that loss of methylation promotes G4 formation and activates alternative promoters in regulatory elements, whereas methylated regions lack these functions.
Our findings provide new insights into the mechanistic link between MetDs and cancer, highlighting non-B DNA structures as key contributors to disease progression.
The lecture is part of the Bioinformatics Seminar Series, which aims to invite exciting speakers working on the current state-of-the-art bioinformatics problems.