Insight into the epigenetic regulation of gene expression in the bloodstream and procyclic forms of Trypanosoma brucei 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 Trypanosoma brucei brucei. 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 T. brucei and may help inform future approaches for managing parasitic infections.