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

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