CCAAT/enhancer-binding protein (C/EBP) β is acetylated at multiple lysines -: Acetylation of C/EBP β at lysine 39 modulates its ability to activate transcription

Transcription factor function can be modulated by post-translational modifications. Because the transcription factor CCAAT/enhancer-binding protein (C/EBP) beta associates with the nuclear coactivator p300, which contains acetyltransferase activity, acetylation of C/EBP beta was examined to understand its regulation and function. C/EBP beta is acetylated by acetyltransferases p300 and p300/CREB-binding protein associated factor. Endogenous C/EBP beta in 3T3-F442A preadipocytes is also recognized by an acetyl-lysine-specific antibody. Analysis of truncations of C/EBP beta and peptides based on C/EBP beta sequences identified multiple lysines within C/EBP beta that can be acetylated. Among these, a novel acetylation site at lysine 39 of C/EBP beta was identified. Mutation of Lys-39 to arginine or alanine impairs its acetylation and the ability of C/EBP beta to activate transcription at the promoters for C/EBP beta and c-fos. Different C/EBP beta-responsive promoters require different patterns of acetylated lysines in C/EBP beta for transcription activation. Furthermore, C/EBP beta acetylation was increased by growth hormone, and mutation of Lys-39 impaired growth hormone-stimulated c-fos promoter activation. These data suggest that acetylation of Lys-39 of C/EBP beta, alone or in combination with acetylation at other lysines, may play a role in C/EBP beta-mediated transcriptional activation.