Dittmar G, Hernandez DP, Kowenz-Leutz E, Kirchner M, Kahlert G, Wesolowski R, Baum K, Knoblich M, Hofstaetter M, Muller A, Wolf J, Reimer U, Leutz A

CCAAT enhancer-binding protein beta (C/EBP?) is a pioneer transcription factor that specifies cell differentiation. C/EBP? is intrinsically unstructured, a molecular feature common to many proteins involved in signal processing and epigenetics. The structure of C/EBP? differs depending on alternative translation initiation and multiple post-translational modifications (PTM). Mutation of distinct PTM ...

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sites in C/EBP? alters protein interactions and cell differentiation, suggesting that a C/EBP? PTM indexing code determines epigenetic outcomes. Herein, we systematically explored the interactome of C/EBP? using an array technique based on spot-synthesized C/EBP?-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/EBP? 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.

Date: Mar. 29, 2019

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