MPI Campus Seminar: Structural insights into pioneer transcription factor interactions with chromatin

MPI Campus Seminar

  • Datum: 13.01.2021
  • Uhrzeit: 11:00 - 12:00
  • Vortragende(r): Svetlana Dodonova
  • Department of Molecular Biology
  • Ort: Max-Planck-Institut für biophysikalische Chemie (MPIBPC)
  • Raum: Online
  • Gastgeber: S. Glöggler, A. Godec, A. Faesen, J. Liepe, S. Meek, A. Stein, M. Wilczek, S. Karpitschka, D. Zwicker, M. Oudelaar, L. Andreas
  • Kontakt: stefan.gloeggler@mpibpc.mpg.de
MPI Campus Seminar: Structural insights into pioneer transcription factor interactions with chromatin
The activity of the human genome is controlled by more than 1,600 transcription factors. These factors recognize DNA elements and recruit proteins to regulate gene activity. Most of them only bind free DNA that it is not wrapped up into chromatin. Only so-called pioneer factors can bind chromatin directly, they do so via contacts to its nucleosome units. Pioneer factors are required for stem cell pluripotency, embryo development, and cell differentiation. But it is poorly understood how they engage with chromatin and trigger cell type conversion.
A prominent pioneer factor is SOX2 which interacts with nucleosomes and can trigger chromatin opening. There are over a dozen factors in the SOX family that are essential for development.
We report structures of the DNA-binding domains of SOX2 and SOX11 pioneer factors bound to nucleosomes – the first structures of pioneer factor complexes with nucleosomes to date (Dodonova et al., 2020). We find that SOX factors can bind and locally distort DNA on both sides of the nucleosomal disc. SOX factor binding also facilitates detachment of terminal nucleosomal DNA and thereby increases DNA accessibility. SOX factors furthermore trigger a repositioning of the N-terminal region of histone H4. This is predicted to interfere with the stacking of nucleosomes and higher-order chromatin structure. Traditionally, pioneer factors were thought to mark chromatin regions and recruit other factors that can slide, evict, and modify nucleosomes. Our results, however, indicate that pioneer factors can to some extent also initiate chromatin opening themselves.
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