TY - JOUR
T1 - PRISMA and BioID disclose a motifs-based interactome of the intrinsically disordered transcription factor C/EBPα
AU - Ramberger, Evelyn
AU - Sapozhnikova, Valeria
AU - Kowenz-Leutz, Elisabeth
AU - Zimmermann, Karin
AU - Nicot, Nathalie
AU - Nazarov, Petr V.
AU - Perez-Hernandez, Daniel
AU - Reimer, Ulf
AU - Mertins, Philipp
AU - Dittmar, Gunnar
AU - Leutz, Achim
N1 - Funding Information:
We thank Tommaso Mari and Marieluise Kirchner for scientific discussions. E.R. was supported by a fellowship of the Berlin School of Integrated Oncology (BSIO). The project was partially supported by a grant to A.L., DFG , LE 770/4-2. Parts of figures were created with BioRender.com .
Publisher Copyright:
© 2021
PY - 2021/6/25
Y1 - 2021/6/25
N2 - 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.
AB - 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.
KW - Omics
KW - Proteomics
KW - Transcriptomics
UR - https://www.scopus.com/pages/publications/85108084516
U2 - 10.1016/j.isci.2021.102686
DO - 10.1016/j.isci.2021.102686
M3 - Article
C2 - 34189442
AN - SCOPUS:85108084516
SN - 2589-0042
VL - 24
SP - 102686
JO - iScience
JF - iScience
IS - 6
M1 - 102686
ER -