Histone acetyltransferase activity of p300 enhances the activation of IL-12 p40 promoter

被引:17
作者
Sun, Haijing [1 ]
Lu, Jun [1 ]
Wei, Liang [1 ]
Wang, Xiuli [1 ]
Xu, Xin [1 ]
Dong, Mei [1 ]
Huang, Baiqu [1 ]
机构
[1] NE Normal Univ, Inst Cytol & Genet, Changchun 130024, Peoples R China
基金
中国国家自然科学基金;
关键词
histone acetyltransferase; interleukin-12; p300; c-Rel;
D O I
10.1016/j.molimm.2004.05.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukin-12 (IL-12) is a heterodimeric cytokine produced by macrophages in response to intracellular pathogens and provides an obligatory signal for the differentiation of T-helper-1 cells. p300 is an important histone acetyltransferase (HAT) and has been implicated in the regulation of gene expression. Whether p300 plays a role in the IL-12 expression has not been investigated before. In this study, we analyzed the roles of p300 in the regulation of human IL-12 p40. By using RT-PCR and a series of co-transfection studies, we found that p300 had a stimulating effect on the expression of endogenous IL-12 p40 mRNA and on the activity of IL-12 p40 promoter. We also showed that the HAT activity of p300 was essential to its function in regulating IL-12 promoter, since the mutant p300 with the HAT domain deleted did not have such a stimulation effect. In addition, the adenovirus E1A protein suppressed the p300 function, whereas the mutant E1A lacking the p300 interaction domain did not. Furthermore, p300 was able to reinforce the c-Rel-mediated activation of IL-12 p40. Results presented in this paper implicate that p300 is involved in the transcriptional regulation of IL-12 p40, and IL-12 p40 is one of the target genes of p300. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1241 / 1246
页数:6
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