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

Elisabeth Kowenz-Leutz, Ole Pless, Gunnar Dittmar, Maria Knoblich, Achim Leutz*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

73 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1105-1115
Number of pages11
JournalEMBO Journal
Volume29
Issue number6
DOIs
Publication statusPublished - Mar 2010
Externally publishedYes

Keywords

  • Chromatin remodelling
  • Differentiation
  • Histone code
  • Post-translational modification
  • Signalling

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