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Sp1 deacetylation induced by phorbol ester recruits p300 to activate 12(S)-lipoxygenase gene transcription
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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. 相似文献
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Huang W Zhao S Ammanamanchi S Brattain M Venkatasubbarao K Freeman JW 《The Journal of biological chemistry》2005,280(11):10047-10054
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Schnur N Seuter S Katryniok C Rådmark O Steinhilber D 《Biochimica et biophysica acta》2007,1771(10):1271-1282
The histone deacetylase inhibitor trichostatin A (TsA) potently induces 5-lipoxygenase (5-LO) promoter activity in reporter gene assays as well as 5-LO mRNA expression. We identified two proximal Sp1/Sp3 binding sites in the 5-LO gene promoter mediating the TsA effect in both 5-LO-negative HeLa cells and in 5-LO expressing Mono Mac 6 (MM6) cells, the tandem GC-boxes, by contrast, were not important for the TsA effect. TsA neither altered the protein expression levels of Sp1/Sp3 nor of the histone deacetylases HDAC1/2, nor did it apparently change the protein complex formation by these factors. Also, treatment of cells with TsA did not change the binding affinity of Sp1/Sp3 in cell extracts, as tested by DAPA analysis using probes containing the proximal GC boxes. However, in the living cell TsA induced Sp1, Sp3 and RNA polymerase II recruitment to the 5-LO promoter without changing the acetylation status of histone protein H4. Cotransfection studies suggest that both Sp1 and Sp3 can mediate the TsA effect. This is the first report demonstrating that Sp3 is involved in the regulation of 5-LO promoter activity. In summary, we show that TsA increases 5-LO promoter activity by the enhanced recruitment of Sp1 and Sp3 to the 5-LO promoter. 相似文献
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The human pituitary tumor transforming gene (hPTTG) serves as a marker for malignancy grading in several cancers, hPTTG is in volved in multiple cellular pathways including cell transformation, apoptosis, DNA repair, genomic instability, mitotic control and angiogenesis induction. However, the molecular mechanisms underlying hPTTG regulation have not been fully explored. In this study, we found that overexpression of histone acetyltransferase (HAT) p300 upregulated hPTTG at the levels of promoter activity, mRNA and protein expression. Moreover, the HAT activity of p300 was critical for its regulatory function. Chromatin immunoprecipitation (ChIP)analysis revealed that overexpression of p300 elevated the level of histone H3 acetylation on the hPTTG promoter. Additionally, the NF-Y sites at the hPTTG promoter exhibited a synergistic effect on upregulation of hPTTG through interacting with p300. We also found thattreatment of 293T cells with the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) increased hPTTG promoter activity. Meanwhile, we provided evidence that HDAC3 decreased hPTTG promoter activity. These data implicate an important role of the histone acetylation modification in the regulation of hPTTG. 相似文献