Acetylation and deacetylation regulate CCAAT/enhancer binding protein β at K39 in mediating gene transcription

The transcription factor CCAAT/enhancer binding protein beta (C/EBP beta) contains multiple acetylation sites, including lysine (K) 39. Mutation of C/EBP beta at K39, an acetylation site in the transcriptional activation domain, impairs transcription of C/EBP beta target genes in a dominant-negative fashion. Further, K39 of C/EBP beta can be cleacetylated by HDAC1, and HDAC1 may decrease C/EBP beta-mediated transcription, suggesting that acetylation of C/EBP beta at K39 is dynamically regulated in mediating gene transcription. Acetylation of endogenous C/EBP beta at K39 is detected in adipose tissue, and also occurs in 3T3-L1 cells undergoing adipocyte conversion. In addition, mutation of K39 in C/EBP beta impairs activation of its target genes encoding C/EBP alpha. and PPAR gamma, essential mediators of adipogenesis, as well as adipocyte genes for leptin and Glut4. These findings suggest that acetylation of C/EBP beta at K39 is an important and dynamic regulatory event that contributes to its ability to transactivate target genes, including those associated with adipogenesis and adipocyte function. (C) 2008 Elsevier Ireland Ltd. All rights reserved.