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

Evelyn Ramberger, Valeria Sapozhnikova, Elisabeth Kowenz-Leutz, Karin Zimmermann, Nathalie Nicot, Petr V. Nazarov, Daniel Perez-Hernandez, Ulf Reimer, Philipp Mertins, Gunnar Dittmar, Achim Leutz*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number102686
Pages (from-to)102686
JournaliScience
Volume24
Issue number6
DOIs
Publication statusPublished - 25 Jun 2021

Keywords

  • Omics
  • Proteomics
  • Transcriptomics

Fingerprint

Dive into the research topics of 'PRISMA and BioID disclose a motifs-based interactome of the intrinsically disordered transcription factor C/EBPα'. Together they form a unique fingerprint.

Cite this