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

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Item Type:Article
Title:PRISMA and BioID disclose a motifs-based interactome of the intrinsically disordered transcription factor C/EBPα
Creators Name:Ramberger, E. and Sapozhnikova, V. and Kowenz-Leutz, E. and Zimmermann, K. and Nicot, N. and Nazarov, P.V. and Perez-Hernandez, D. and Reimer, U. and Mertins, P. and Dittmar, G. and Leutz, A.
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.
Source:iScience
ISSN:2589-0042
Publisher:Cell Press
Volume:24
Number:6
Page Range:102686
Date:25 June 2021
Official Publication:https://doi.org/10.1016/j.isci.2021.102686
PubMed:View item in PubMed

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