Open AccessGlucocorticoid-stimulated preadipocyte differentiation is mediated through acetylation of C/EBPβ by GCN5
Author(s) -
Nadine WiperBergeron,
Houssein Abdou Salem,
Julianna J. Tomlinson,
Dongmei Wu,
Robert J.G. Haché
Publication year - 2007
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0607378104
Subject(s) - acetylation , ccaat enhancer binding proteins , pcaf , p300 cbp transcription factors , hdac1 , transcription factor , microbiology and biotechnology , lysine , bromodomain , chemistry , biology , histone , hdac4 , biochemistry , nuclear protein , histone deacetylase , gene , amino acid , histone acetyltransferases , histone methyltransferase
Preadipocyte differentiation in culture is driven by an insulin and cAMP dependant transcriptional cascade which induces the bzip transcription factors C/EBPβ and C/EBPδ. We have previously shown that glucocorticoid treatment, which strongly potentiates this differentiation pathway, stimulates the titration of the corepressor histone deacetylase 1 (HDAC1) from C/EBPβ. This results in a dramatic enhancement of C/EBPβ-dependent transcription from the C/EBPα promoter, concomitant with potentiation of preadipocyte differentiation. Here, we show that C/EBPβ is acetylated by GCN5 and PCAF within a cluster of lysine residues between amino acids 98–102 and that this acetylation is strongly induced by glucocorticoid treatment. Arginine substitution of the lysine residues within the acetylation motif of C/EBPβ prevented acetylation and blocked the ability of glucocorticoids to enhance C/EBPβ-directed transcription and to potentiate C/EBPβ-dependent preadipocyte differentiation. Moreover, acetylation of C/EBPβ appeared to directly interfere with the interaction of HDAC1 with C/EBPβ, suggesting that PCAF/GCN5-dependent acetylation of C/EBPβ serves as an important molecular switch in determining the transcriptional regulatory potential of this transcription factor.