Dataset Information

Combined Peptide array screen and proximity labeling proteomics fine map C/EBPa protein interactions

ABSTRACT: The pioneering transcription factor C/EBPα coordinates cell fate and cell differentiation. The structure of C/EBPα comprises intrinsically disordered regions, multiple short linear motifs, and extensive post-translational side chain modifications (PTM), reflecting its modularity and functional plasticity. Here, we combined peptide matrix screening with biotin ligase proximity labeling proteomics to generate a PTM-dependent comprehensive protein interaction map of C/EBPα in myeloid cells. We found that protein interactions hotspots coincide with homologous conserved regions of the C/EBP family. PTMs alter the interaction spectrum of multi-valent C/EBP-motifs to configure a dynamic C/EBPα hub that selects co-regulatory components such as of the BAF/SWI-SNF complexes in an C/EBPα arginine-methylation and isoform state specific fashion. Our data suggest that the functional plasticity of C/EBPs is based on promiscuous interactions with protein machineries involved in gene regulation, epigenetics, genome organization, DNA replication, RNA processing and transport. The experimental strategy opens new avenues to systematically examine the PTM-dependent interactome of intrinsically disordered proteins as a basis to explore their multi-modal functions.

INSTRUMENT(S): Q Exactive Plus, Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Leukocyte, Cell Culture

SUBMITTER: Evelyn Ramberger

LAB HEAD: Philipp Mertins

PROVIDER: PXD022903 | Pride | 2021-07-12

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Animal_20180904_ER_BioID_NB4_BirA_1.raw	Raw
	Animal_20180904_ER_BioID_NB4_BirA_2.raw	Raw
	Animal_20180904_ER_BioID_NB4_WT_1.raw	Raw
	Animal_20180904_ER_BioID_NB4_WT_2.raw	Raw
	Animal_20180904_ER_BioID_NB4_WT_3.raw	Raw

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Publications

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

Ramberger Evelyn E Sapozhnikova Valeria V Kowenz-Leutz Elisabeth E Zimmermann Karin K Nicot Nathalie N Nazarov Petr V PV Perez-Hernandez Daniel D Reimer Ulf U Mertins Philipp P Dittmar Gunnar G Leutz Achim A

iScience 20210604 6

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 <i>in vivo</i> validated and isoform specific interaction map of C/EBPα. The myeloid C/EBPα interactome comprises ...[more]

PMID: 34189442

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