Sp1 deacetylation induced by phorbol ester recruits p300 to activate 12(S)-lipoxygenase gene transcription.
We previous reported that Sp1 recruits c-Jun to the promoter of the 12(S)-lipoxygenase gene in 12-myristate 13-acetate-treated cells. We now show that Sp1 that recruited HDAC1 to the Sp1/cJun complex was constitutively acetylated when cells were exposed to phorbol 12-myristate 13-acetate (PMA) (3 h). Prolonged stimulation of the cells with PMA (9 h), however, caused the dissociation of histone deacetylase 1 (HDAC1) and the deacetylation of Sp1, with the latter being able to recruit p300 that in turn caused the acetylation and dissociation of histone 3, thus enhancing the expression of 12(S)-lipoxygenase. We also overexpressed an Sp1 mutant (K703/A, lacking acetylation sites) in the cell and found that cells recruited more p300 and expressed more 12(S)-lipoxygenase. Taken together, our results indicated that Sp1 recruits HDAC1 together with c-Jun to the gene promoter, followed by deacetylation of Sp1 upon PMA treatment. p300 is then recruited to the gene promoter through the interaction with deacetylated Sp1 to acetylate histone 3, leading to the enhancement of the expression of 12(S)-lipoxygenase.
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, Republic of China.
Jan-Jong
JJ
Hung
Yi-Ting
YT
Wang
Wen-Chang
WC
Chang
D000107:Acetylation; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D050881:E1A-Associated p300 Protein / Q000187:drug effects / Q000378:metabolism*; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic
D016329:Sp1 Transcription Factor; D001092:Arachidonate 12-Lipoxygenase; D050881:E1A-Associated p300 Protein; D048031:JNK Mitogen-Activated Protein Kinases; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D008239:Lysine; D013755:Tetradecanoylphorbol Acetate