Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster V41
Höfundar / Authors: Sveinn Bjarnason (1), Jens Nicolai Vilstrup Decker (2), Eliška Koutná (3), Kinga S. Demény (1), Vaclav Veverka (3), Pétur O. Heidarsson (1,2)
Starfsvettvangur / Affiliations: 1. Department of Biochemistry, Science Institute, University of Iceland, Sturlugata 7, 102 Reykjavík, Iceland. 2. Department of Biology, Section for Biomolecular Sciences, University of Copenhagen, Ole Maaløes Vej 5, 2200 København N., Denmark. 3. Department of Cell Biology, Faculty of Science, Charles University, Albertov 6, 128 00 Prague 2, Czech Republic.
Kynnir / Presenter: Sveinn Bjarnason
Through their interaction with chromatin, pioneer transcription factors not only initiate gene expression changes essential for development but also serve as key regulators in cellular reprogramming and disease processes. The process by which the pioneer transcription factor Sox2 remodels nucleosomes remains poorly understood. Similarly, the structural configuration of Sox2’s intrinsically disordered regions (IDRs) when engaged with nucleosomes, and the subsequent effects on nucleosome conformation, are not well defined. To address these gaps, we employed smFRET and NMR spectroscopy to elucidate the conformations of Sox2 in complex with nucleosomes. We explore its binding modes, the location dependent affinity of binding sites and the resulting structural impacts on the nucleosome itself. Our findings reveal that Sox2’s IDR extends significantly upon interaction with the nucleosome, and we identify a specific interaction site within the IDR. Interestingly, Sox2 preferentially binds non-specifically to nucleosome linkers, even when specific binding sites are placed in various locations on the core nucleosome. Sox2’s IDR not only affects Sox2’s binding affinity when binding to the core nucleosome, but also the degree of remodeling. Identifying an interaction site within Sox2’s IDRs marks a step forward in our grasp of pioneer transcription factor mechanism, and we are now leveraging this insight to design improved Sox2 variants with enhanced cellular reprogramming abilities.