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Item Type: | Article |
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Title: | Crosstalk between C/EBPbeta phosphorylation, arginine methylation, and SWI/SNF/Mediator implies an indexing transcription factor code |
Creators Name: | Kowenz-Leutz, E., Pless, O., Dittmar, G., Knoblich, M. and Leutz, A. |
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. |
Keywords: | Chromatin Remodelling, Differentiation, Histone Code, Post-Translational Modification, Signalling, Animals, Mice |
Source: | EMBO Journal |
ISSN: | 0261-4189 |
Publisher: | Nature Publishing Group |
Volume: | 29 |
Number: | 6 |
Page Range: | 1105-1115 |
Date: | 17 March 2010 |
Official Publication: | https://doi.org/10.1038/emboj.2010.3 |
PubMed: | View item in PubMed |
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