G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta.
Article Details
- CitationCopy to clipboard
Pless O, Kowenz-Leutz E, Knoblich M, Lausen J, Beyermann M, Walsh MJ, Leutz A
G9a-mediated lysine methylation alters the function of CCAAT/enhancer-binding protein-beta.
J Biol Chem. 2008 Sep 26;283(39):26357-63. doi: 10.1074/jbc.M802132200. Epub 2008 Jul 21.
- PubMed ID
- 18647749 [ View in PubMed]
- Abstract
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.