Málstofa Lífvísindaseturs - Insights into Sox2 - Mediated Chromatin Remodeling

Málstofa Lífvísindaseturs fimmtudaginn 15. maí kl. 12:30-13:10 í Árnagarði, stofu 201

Fyrirlesari: Dr. Sveinn Bjarnason, nýdoktor, Líf- og umhverfisvísindadeild, Lífefnafræðistofa, Háskóla Íslands.

Titill: Structural and Functional Insights into Sox2-Mediated Chromatin Remodeling

Ágrip: 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 and its capacity to displace histone H1 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 single molecule Förster Resonance Energy Transfer (smFRET) and Nuclear Magnetic Resonance (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. Surprisingly, Sox2’s IDR not only affects Sox2’s binding affinity when binding to the core nucleosome, but also the degree of remodeling. Moreover, our data not only shows Sox2’s capability to displace linker histone H1, highlighting a critical mechanism in chromatin remodeling, but also demonstrates how this activity aligns with broader strategies employed by pioneer transcription factors to engage and remodel chromatin. 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.