Chromatin Biology: Pioneer transcription factors
Genome chromatinization regulates transcription by posing physical barriers to the activity of RNA Polymerase II, and to the binding of transcription factors (TFs). Access to gene promoters is attained via a complex interplay between TFs, transcriptional co-regulators (co-activators and co-repressors), which recognize and alter histone-modifications, and chromatin remodelers. The Thomä lab utilizes a combination of structural techniques, biochemistry and functional assays to dissect how the position and orientation of specific DNA motifs on nucleosomes controls TF binding, and how these complexes are then further decoded by co-regulators. To this end, we have investigated how the TFs OCT4-SOX2 (Michael, Grand, Isbel et al, Science, 2020), MYC-MAX and CLOCK-BMAL1 engage nucleosomes in different positions. We could show that these TFs trigger DNA distortions by recognizing partial motifs or DNA release to make site-specific histone contacts. Ongoing work is aimed at understanding how TF chromatin occupancy influences upstream and downstream transcription regulation pathways.
(Mark et al. 2023; Pla-Prats et al. 2023) and chromatin biology (Matsumoto et al. 2019) with work on transcription (Tsai et al. 2023; Michael et al. 2023) and molecular glues (Sievers et al. 2018; Słabicki et al. 2020). As such, we have a long-standing interest in pioneer transcription factors and transcriptional repressors (Michael et al. 2020; 2023).