| Autor: |
Ramberger, E., Sapozhnikova, V., Kowenz-Leutz, E., Zimmermann, K., Nicot, N., Nazarov, P.V., Perez-Hernandez, D., Reimer, U., Mertins, P., Dittmar, G., Leutz, A. |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
The pioneering transcription factor C/EBPα coordinates cell fate and cell differentiation. C/EBPα represents an intrinsically disordered protein with multiple short linear motifs and extensive post-translational side chain modifications (PTM), reflecting its modularity and functional plasticity. Here, we combined arrayed peptide matrix screening (PRISMA) with biotin ligase proximity labeling proteomics (BioID) to generate a linear, isoform specific and PTM-dependent protein interaction map of C/EBPα in myeloid cells. The 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 as the basis of functional C/EBPα plasticity. Protein interaction hotspots were identified that coincide with homologous conserved regions of the C/EBP family and revealed interaction motifs that score as molecular recognition features (MoRF). PTMs alter the interaction spectrum of multi-valent C/EBP-motifs to configure a multimodal transcription factor hub that allows interaction with multiple co-regulatory components, including BAF/SWI-SNF or Mediator complexes. Combining PRISMA and BioID acts as a powerful strategy to systematically explore the interactomes of intrinsically disordered proteins and their PTM-regulated, multimodal capacity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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