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G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta

Item Type:Article
Title:G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta
Creators Name:Pless, O. and Kowenz-Leutz, E. and Knoblich, M. and Lausen, J. and Beyerman, M. and Walsh, M.J. and Leutz, A.
Abstract:The functional capacity of the transcriptional regulatory CCAAT/Enhancer Binding Protein (C/EBP) ss is governed by protein interactions and post-translational protein modifications. In a proteome wide interaction screen, the histone-lysine N-methyltransferase, H3 lysine-9 specific 3 (G9a) was found to directly interact with the C/EBPss transactivation domain (TAD). Binding between G9a and C/EBPss was confirmed by GST-pulldown and co-immunoprecipitation. Metabolic labeling showed that C/EBPss is post-translationally modified by methylation in vivo. A conserved lysine residue in the C/EBPss-TAD served as a substrate for G9a mediated methylation. G9a, but not a methyltransferase defective G9a mutant, abrogated the transactivation potential of wild type C/EBPss. A C/EBPss TAD mutant that contained a lysine to alanine exchange was resistant to G9a mediated inhibition. Moreover, the same mutation conferred super-activation of a chromatin embedded, endogenous C/EBPss target gene. Our data identify C/EBPss as a direct substrate of G9a-mediated post-translational modification that alters the functional properties of C/EBPss during gene regulation.
Keywords:CCAAT-Enhancer-Binding Protein-beta, Hela Cells, Histocompatibility Antigens, Histone-Lysine N-Methyltransferase, Mutation, Post-Translational Protein Processing, Tertiary Protein Structure, Proteome, Transcriptional Activation
Source:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology
Page Range:26357-26363
Date:26 September 2008
Official Publication:https://doi.org/10.1074/jbc.M802132200
PubMed:View item in PubMed

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