STAT4 is required for interleukin-12-induced chromatin remodeling of the CD25 locus
STAT4 is required for interleukin-12-induced chromatin remodeling of the CD25 locus
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DOI：
10.1074/jbc.m309979200
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发表时间：
2004-02-20
影响因子：
4.8
通讯作者：
Kaplan, MH
中科院分区：
文献类型：
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作者：
O'Sullivan, A;Chang, HC;Kaplan, MH
信号转导器和转录激活剂 4 (STAT4) 是白细胞介素 12 (IL-12) 刺激的炎症免疫反应的关键介质。尽管对 STAT4 缺陷小鼠的免疫反应进行了广泛分析，但对 STAT4 依赖性基因诱导的了解仍然很少。 IL-12 刺激 IL-2 受体 a 链基因 (CD25) mRNA 水平和表面表达的增加需要 STAT4。在本报告中，我们利用染色质免疫沉淀分析来分析 CD25 基因染色质重塑中 IL-12 刺激和 STAT4 依赖性变化。基因激活需要 STAT4 与 PRRIII 上游调控元件结合、招募 CREB 结合蛋白 (CBP) 以及染色质重塑，包括 CD25 启动子内组蛋白的乙酰化增加和甲基化减少。有证据表明 STAT4 还促进其他因子与 CD25 启动子（包括 c-Jun）的结合。因此，这些结果提供了 STAT4 依赖性基因诱导的模型和细胞因子诱导的 CD25 基因表达的机制。
Signal transducer and activator of transcription 4 (STAT4) is a critical mediator of interleukin-12 (IL-12)stimulated inflammatory immune responses. Despite extensive analysis of the immune responses of STAT4-deficient mice, there is still very little understood about STAT4-dependent gene induction. IL-12 stimulated increases in IL-2 receptor a chain gene (CD25) mRNA levels and surface expression require STAT4. In this report, we utilize chromatin immunoprecipitation assays to analyze IL-12-stimulated and STAT4-dependent changes in chromatin remodeling of the CD25 gene. Gene activation requires binding of STAT4 to the PRRIII upstream regulatory element, the recruitment of the CREB-binding protein (CBP), and chromatin remodeling including increased acetylation and decreased methylation of histones within the CD25 promoter. Evidence suggests that STAT4 also facilitates binding of other factors to the CD25 promoter including c-Jun. Thus, these results provide a model for STAT4-dependent gene induction and a mechanism for cytokine-induced expression of the CD25 gene.