Determinants for chromatin accessibility upon transcription factor binding

• Applicant: Professor Dr. Gunnar Schotta
• Subject Area: General Genetics and Functional Genome Biology ; Cell Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 542519968

The molecular mechanisms governing the ability of pioneer transcription factors (PTFs) to initiate chromatin opening are largely unknown. Focusing on the pioneer transcription factor Foxa2 we found that only co-binding with other TFs, such as Gata4 lead to increased chromatin accessibility. We have now identified Tet2 as modulator of chromatin accessibility on combinatorial Foxa2/Gata4 binding sites. Notably, Tet2 catalytic activity appears dispensable for chromatin accessibility, prompting an exploration of its non-catalytic functions. Our research plan involves investigating the impact of Tet2 on chromatin modifications, determining recruitment to Foxa2/Gata4 sites, and identifying crucial Tet2 protein domains. Additionally, we aim to unravel the interplay between Tet2 and other proteins at these sites, shedding light on facilitators or repressors of chromatin accessibility. Chemical inhibitors and knockout cell lines will be employed to pinpoint the responsible chromatin remodeling complex. In summary, our project delves into the intricate molecular interactions driving chromatin opening by PTFs, emphasizing Tet2's non-catalytic functions and its orchestration of chromatin accessibility at specific binding sites.

• DFG Programme: Research Grants