Crosstalk between C/EBPβ phosphorylation, arginine methylation, and SWI/SNF/Mediator implies an indexing transcription factor code

• Elisabeth Kowenz-Leutz ^[1] ; Ole Pless ^[1] ; Gunnar Dittmar ^[1] ; Maria Knoblich ^[1] ; Achim Leutz ^[1]
  1. [1] Max Delbrueck Center for Molecular Medicine, Berlin, Germany
• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 29, Nº. 6, 2010, págs. 1105-1115
• Idioma: inglés
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• Resumen

  • Cellular signalling cascades regulate the activity of transcription factors that convert extracellular information into gene regulation. C/EBPβ is a ras/MAPkinase signal-sensitive transcription factor that regulates genes involved in metabolism, proliferation, differentiation, immunity, senescence, and tumourigenesis. The protein arginine methyltransferase 4 PRMT4/CARM1 interacts with C/EBPβ and dimethylates a conserved arginine residue (R3) in the C/EBPβ N-terminal transactivation domain, as identified by mass spectrometry of cell-derived C/EBPβ. Phosphorylation of the C/EBPβ regulatory domain by ras/MAPkinase signalling abrogates the interaction between C/EBPβ and PRMT4/CARM1. Differential proteomic screening, protein interaction studies, and mutational analysis revealed that methylation of R3 constraines interaction with SWI/SNF and Mediator complexes. Mutation of the R3 methylation site alters endogenous myeloid gene expression and adipogenic differentiation. Thus, phosphorylation of the transcription factor C/EBPβ couples ras signalling to arginine methylation and regulates the interaction of C/EBPβ with epigenetic gene regulatory protein complexes during cell differentiation.