Phosphorylation of Histone H3 by Protein Kinase C Signaling Plays a Critical Role in the Regulation of the Developmentally Important TBX2 Gene

• Published in: The Journal of biological chemistry Vol. 284; no. 39; pp. 26368 - 26376
• Main Authors: Teng, Huajian, Ballim, Reyna Deeya, Mowla, Shaheen, Prince, Sharon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.09.2009; American Society for Biochemistry and Molecular Biology
• Subjects: Binding Sites - genetics; Blotting, Western; Cell Line; Chromatin Immunoprecipitation; Data processing; Enzyme Inhibitors - pharmacology; Fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Flavonoids - pharmacology; Gene Expression - drug effects; Histone H3; Histones - metabolism; Humans; Imidazoles - pharmacology; Indoles - pharmacology; Maleimides - pharmacology; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Molecular Basis of Cell and Developmental Biology; Phosphorylation; Promoter Regions, Genetic - genetics; Protein Binding; Protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Pyridines - pharmacology; Recruitment; Reverse Transcriptase Polymerase Chain Reaction; Ribosomal Protein S6 Kinases, 90-kDa - genetics; Ribosomal Protein S6 Kinases, 90-kDa - metabolism; RNA Interference; Serine - metabolism; Signal Transduction; Sp1 protein; Sp1 Transcription Factor - metabolism; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; Tbx2 protein; Tetradecanoylphorbol Acetate - pharmacology; TPA; Transcription; Transcription activation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.021360

The mechanism(s) regulating the expression of the TBX2 gene, a key regulator of development, is poorly understood and thus limits an understanding of its function(s). Here we demonstrate that 12-O-tetradecanoylphorbol-13-acetate (TPA) induces TBX2 expression in normal human fibroblasts in a protein kinase C (PKC)-dependent and MAPK-independent manner. Our data further reveal that TPA activates transcription of TBX2 through activating MSK1, which leads to an increase in phosphorylated histone H3 and the recruitment of Sp1 to the TBX2 gene. In addition, TPA was shown to activate MSK1 in a PKC-dependent and MAPK-independent manner. This study is the first to provide evidence that phosphorylation of histone H3 leads to the transcriptional activation of the TBX2 gene and to link MSK1 to PKC.