Hung Jan-Jong, Wang Yi-Ting, Chang Wen-Chang
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, Republic of China.
Mol Cell Biol. 2006 Mar;26(5):1770-85. doi: 10.1128/MCB.26.5.1770-1785.2006.
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.
我们之前报道过，在经12-肉豆蔻酸13-乙酸酯处理的细胞中，Sp1会将c-Jun招募至12(S)-脂氧合酶基因的启动子区域。我们现在发现，当细胞暴露于佛波酯12-肉豆蔻酸13-乙酸酯（PMA）3小时时，招募HDAC1至Sp1/cJun复合物的Sp1会持续发生乙酰化。然而，用PMA对细胞进行长时间刺激（9小时）会导致组蛋白去乙酰化酶1（HDAC1）解离以及Sp1去乙酰化，后者能够招募p300，进而导致组蛋白3的乙酰化和解离，从而增强12(S)-脂氧合酶的表达。我们还在细胞中过表达了一种Sp1突变体（K703/A，缺乏乙酰化位点），发现细胞招募了更多的p300并表达了更多的12(S)-脂氧合酶。综上所述，我们的结果表明，Sp1与c-Jun一起将HDAC1招募至基因启动子，随后在PMA处理后Sp1发生去乙酰化。然后，p300通过与去乙酰化的Sp1相互作用被招募至基因启动子，使组蛋白3乙酰化，导致12(S)-脂氧合酶表达增强。
