Influence of DNA G-Quadruplexes on Chromatin Accessibility
Research Poster Health & Life Sciences 2025 Graduate ExhibitionPresentation by Leman Simpson
Exhibition Number 143
Abstract
G-quadruplex (G4) structures in DNA have been studied in vitro for decades but their genetic functions have recently come to light. G4 structures have been identified in CG-rich promoters, including many housekeeping gene promoters, which have high chromatin accessibility and transcription levels. However, there is little causative data on the compatibility of G4s and chromatin. Using chromatin molecular biology and DNA library approaches, we seek to understand if G4s can form on a nucleosome, if G4 stability affects chromatin, and the regulatory roles of TFs in maintaining nucleosome-depleted regions near G4s. Current work involves building a molecular toolkit for studying G4’s, preliminary chromatin experiments, and initial use of a high-throughput DNA library approach for determining the sequence characteristics affecting G4/chromatin interplay.
Importance
Non-helical DNA structures have been shown to exist in cellular contexts suggesting a possible regulatory function. While many works now establish correlations between non-helical DNA structures such as G-quadruplexes and DNA accessibility that is associated with transcription, no works have directly tested this correlation. This work seeks to determine whether the mutual exclusivity between G4 DNA and the nucleosome is an intrinsic property or if interactions with other factors maintain this relationship. Characterizing these interactions improves our understanding of the molecular genetics of housekeeping genes and their dysregulation in cancer.