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

Abstract The transcription factor CCAAT/enhancer binding protein β (C/EBPβ) contains multiple acetylation sites, including lysine (K) 39. Mutation of C/EBPβ at K39, an acetylation site in the transcriptional activation domain, impairs transcription of C/EBPβ target genes in a dominant-negative fashion. Further, K39 of C/EBPβ can be deacetylated by HDAC1, and HDAC1 may decrease C/EBPβ-mediated transcription, suggesting that acetylation of C/EBPβ at K39 is dynamically regulated in mediating gene transcription. Acetylation of endogenous C/EBPβ at K39 is detected in adipose tissue, and also occurs in 3T3-L1 cells undergoing adipocyte conversion. In addition, mutation of K39 in C/EBPβ impairs activation of its target genes encoding C/EBPα and PPARγ, essential mediators of adipogenesis, as well as adipocyte genes for leptin and Glut4. These findings suggest that acetylation of C/EBPβ 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.