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

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Official URL:https://doi.org/10.1038/emboj.2010.3
PubMed:View item in PubMed
Creators Name:Kowenz-Leutz, E. and Pless, O. and Dittmar, G. and Knoblich, M. and Leutz, A.
Journal Title:EMBO Journal
Journal Abbreviation:EMBO J
Page Range:1105-1115
Date:17 March 2010
Keywords:Chromatin Remodelling, Differentiation, Histone Code, Post-Translational Modification, Signalling, Animals, Mice
Abstract:Cellular signalling cascades regulate the activity of transcription factors that convert extracellular information into gene regulation. C/EBPbeta 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/EBPbeta and dimethylates a conserved arginine residue (R3) in the C/EBPbeta N-terminal transactivation domain, as identified by mass spectrometry of cell-derived C/EBPbeta. Phosphorylation of the C/EBPbeta regulatory domain by ras/MAPkinase signalling abrogates the interaction between C/EBPbeta 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/EBPbeta couples ras signalling to arginine methylation and regulates the interaction of C/EBPbeta with epigenetic gene regulatory protein complexes during cell differentiation.
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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