Insight into the epigenetic regulation of gene expression in the bloodstream and procyclic forms of <i>Trypanosoma brucei</i> through the involvement of G-quadruplexes

This study explores how G-quadruplexes (G4s) influence gene expression during the transition between bloodstream (BF) and procyclic (PC) forms of <i>Trypanosoma brucei brucei</i>. Computational analysis identified over 115 000 G4-prone sequences, with 63% predicted to form stable G4 structures. These sequences are enriched in regions associated with antigenic variation, suggesting a role in gene regulation. Experimental validation using G4 ligands (AQ1, Pt-TTPY, and pyridostatin) showed a consistent downregulation of differentially expressed genes, supporting the potential relevance of targeting G4s. These results contribute to our understanding of epigenetic regulation in <i>T. brucei</i> and may help inform future approaches for managing parasitic infections.