Cited by 41Advanced Proteomics Techniques and ApplicationsProtein Structure and DynamicsGenomics and Chromatin Dynamics

PRISMA: Protein Interaction Screen on Peptide Matrix Reveals Interaction Footprints and Modifications- Dependent Interactome of Intrinsically Disordered C/EBPβ

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Dittmar, Gunnar, Hernandez, Daniel Perez, Kowenz-Leutz, Elisabeth, Kirchner, Marieluise, Kahlert, Günther, Wesolowski, Radoslaw, Baum, Katharina, Knoblich, Maria +5 more·2019·iScience

Published version of a preprint

Abstract

CCAAT enhancer-binding protein beta (C/EBPβ) is a pioneer transcription factor that specifies cell differentiation. C/EBPβ is intrinsically unstructured, a molecular feature common to many proteins involved in signal processing and epigenetics. The structure of C/EBPβ differs depending on alternative translation initiation and multiple post-translational modifications (PTM). Mutation of distinct PTM sites in C/EBPβ alters protein interactions and cell differentiation, suggesting that a C/EBPβ PTM indexing code determines epigenetic outcomes. Herein, we systematically explored the interactome of C/EBPβ using an array technique based on spot-synthesized C/EBPβ-derived linear tiling peptides with and without PTM, combined with mass spectrometric proteomic analysis of protein interactions. We identified interaction footprints of ∼1,300 proteins in nuclear extracts, many with chromatin modifying, chromatin remodeling, and RNA processing functions. The results suggest that C/EBPβ acts as a multi-tasking molecular switchboard, integrating signal-dependent modifications and structural plasticity to orchestrate interactions with numerous protein complexes directing cell fate and function.

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Authors
Dittmar, G., Hernandez, D. P., Kowenz-Leutz, E., Kirchner, M., Kahlert, G., Wesolowski, R., Baum, K., Knoblich, M., Hofstätter, M., Muller, A., Wolf, J., Reimer, U., & Leutz, A.
Affiliations
  • Max Delbrück Center (DE)
  • Luxembourg Institute of Health (LU)
  • JPT Peptide Technologies (Germany) (DE)
Corresponding author
  • Dittmar, Gunnar
  • Leutz, Achim
Venue
iScience
Publisher
Elsevier BV
Published
2019-03
Volume
13
Pages
351-370
ISSN
2589-0042 (ISSN-L)
OpenAlex
W2921921533
Cited by
41
References
84
Citations by year
2026: 4 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 5 · 2021: 9 · 2020: 2 · 2018: 1
FWCI
1.59
Type
journal article
Language
en
Open access
Locations
  • iScience (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Funders
  • Fonds National de la Recherche Luxembourg
  • Deutsche Forschungsgemeinschaft
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
C/EBPβ, intrinsically disordered proteins, post-translational modification, protein-protein interaction network, pioneer transcription factors, chromatin modification, chromatin remodeling, RNA processing, cell differentiation, epigenetics, structural plasticity

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