Document Detail


G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta.
MedLine Citation:
PMID:  18647749     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The functional capacity of the transcriptional regulatory CCAAT/enhancer-binding protein-beta (C/EBPbeta) 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/EBPbeta transactivation domain (TAD). Binding between G9a and C/EBPbeta was confirmed by glutathione S-transferase pulldown and co-immunoprecipitation. Metabolic labeling showed that C/EBPbeta is post-translationally modified by methylation in vivo. A conserved lysine residue in the C/EBPbeta 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/EBPbeta. A C/EBPbeta 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/EBPbeta target gene. Our data identify C/EBPbeta as a direct substrate of G9a-mediated post-translational modification that alters the functional properties of C/EBPbeta during gene regulation.
Authors:
Ole Pless; Elisabeth Kowenz-Leutz; Maria Knoblich; Jörn Lausen; Michael Beyermann; Martin J Walsh; Achim Leutz
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Publication Detail:
Type:  Journal Article     Date:  2008-07-21
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-22     Completed Date:  2008-11-10     Revised Date:  2012-01-18    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  26357-63     Citation Subset:  IM    
Affiliation:
Max Delbrück Center for Molecular Medicine, Humboldt University of Berlin, Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
CCAAT-Enhancer-Binding Protein-beta / genetics,  metabolism*
HeLa Cells
Histocompatibility Antigens / genetics,  metabolism*
Histone-Lysine N-Methyltransferase / genetics,  metabolism*
Humans
Mutation
Protein Processing, Post-Translational / physiology*
Protein Structure, Tertiary / physiology
Proteome / genetics,  metabolism*
Transcriptional Activation / physiology*
Chemical
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Protein-beta; 0/Histocompatibility Antigens; 0/Proteome; EC 2.1.1.43/EHMT2 protein, human; EC 2.1.1.43/Histone-Lysine N-Methyltransferase

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