Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2021

Erindi/veggspjald / Talk/poster E48

Conformational dynamics of pioneer factor Sox2 during nucleosome remodelling

Höfundar / Authors: Sveinn Bjarnason(1,2), Mahtab Hafizi Yazdabadi(1,2), Matthías Már Valdimarsson(1,2), Kinga Sofia Demény(1,2), Sarah Frederiksen Ruidiaz(1,2), Pétur Orri Heiðarsson(1,2)

Starfsvettvangur / Affiliations: 1. Science Institute, Department of Biochemistry, University of Iceland 2. Biomedical Center, University of Iceland

Kynnir / Presenter: Sveinn Bjarnason

Sox2 is a pioneer transcription factor (pTFs) that has the unique ability to initiate cell fate changes by targeting and remodelling condensed, nucleosome-rich chromatin. Like most transcription factors Sox2 consists of a small, structured DNA binding domain (DBD) and long intrinsically disordered regions (IDRs) including the transactivation domain. Little is known about the molecular mechanism of nucleosome binding and opening, and whether the disordered regions are involved. To elucidate the function of the IDRs we take an integrative approach using single-molecule spectroscopy in combination with FRET (smFRET), nuclear magnetic resonance (NMR) spectroscopy and molecular simulations. Using smFRET, we found that Sox2 can bind to both free and histone H1-bound nucleosomes, leading to an open state of the nucleosome. The presence of histone H1 reduces the affinity of Sox2 by two orders of magnitude, possibly via a protective mechanism by the H1 disordered domains. Furthermore, we found that the IDRs of Sox2 maintain a rather collapsed conformation in the free state, and extend upon binding DNA/nucleosomes. Preliminary NMR data indicate that there are specific interactions between the IDRs in the C-terminal with the structured DBD that qualitatively agree with smFRET data and Alphafold predictions. The picture that emerges from our research reveals a complex conformational behaviour of both Sox2 and nucleosomes suggesting that a sophisticated molecular mechanism underlies pioneer activity. By using a synergistic methodological approach, we aim to understand the pioneering mechanism of this master transcription factor which may impact designs of strategies to control cell identity.