PRISMA and BioID disclose a motifs-based interactome of the intrinsically disordered transcription factor C/EBPα


  • E. Ramberger
  • V. Sapozhnikova
  • E. Kowenz-Leutz
  • K. Zimmermann
  • N. Nicot
  • P.V. Nazarov
  • D. Perez-Hernandez
  • U. Reimer
  • P. Mertins
  • G. Dittmar
  • A. Leutz


  • iScience


  • iScience 24 (6): 102686


  • C/EBPα represents a paradigm intrinsically disordered transcription factor containing short linear motifs and post-translational modifications (PTM). Unraveling C/EBPα protein interaction networks is a prerequisite for understanding the multi-modal functions of C/EBPα in hematopoiesis and leukemia. Here, we combined arrayed peptide matrix screening (PRISMA) with BioID to generate an in vivo validated and isoform specific interaction map of C/EBPα. The myeloid C/EBPα interactome comprises promiscuous and PTM-regulated interactions with protein machineries involved in gene expression, epigenetics, genome organization, DNA replication, RNA processing, and nuclear transport. C/EBPα interaction hotspots coincide with homologous conserved regions of the C/EBP family that also score as molecular recognition features. PTMs alter the interaction spectrum of C/EBP-motifs to configure a multi-valent transcription factor hub that interacts with multiple co-regulatory components, including BAF/SWI-SNF or Mediator complexes. Combining PRISMA and BioID is a powerful strategy to systematically explore the PTM-regulated interactomes of intrinsically disordered transcription factors.