The human IL-2 gene promoter can assemble a positioned nucleosome that becomes remodeled upon T cell activation
The human IL-2 gene promoter can assemble a positioned nucleosome that becomes remodeled upon T cell activation
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DOI：
10.4049/jimmunol.169.5.2466
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发表时间：
2002-09-01
影响因子：
4.4
通讯作者：
Shannon, AF
中科院分区：
文献类型：
--
作者：
Attema, JL;Reeves, R;Shannon, AF
细胞因子 IL-2 的受控产生在哺乳动物免疫系统中发挥着关键作用。该基因的表达受到严格调控，在静息 T 细胞中检测不到表达，并且在 T 细胞激活后出现强烈诱导。 IL-2 近端启动子（+1 至 -300）包含许多明确的转录激活元件，可对 T 细胞刺激做出反应。为了确定染色质结构在白细胞介素 2 基因转录调节中的作用，使用体外染色质重建测定检查了跨 IL-2 启动子区域的核小体组装。 IL-2 启动子组装一个可平移和旋转定位的核小体，跨越一些主要的功能控制元件。转录因子与这些元件的结合（结构蛋白 HMGA1 除外）因核小体的存在而被阻断。对 Jurkat T 细胞中 IL-2 基因染色质结构的分析为体内存在类似位置的核小体提供了证据。 Jurkat T 细胞激活后，该核小体包围的区域会发生重塑。这些观察结果表明，跨 IL-2 近端启动子的定位核小体的存在可能在维持静息 T 细胞中的非活性基因方面发挥重要作用，并且该核小体的重塑对于基因激活很重要。
Controlled production of the cytokine IL-2 plays a key role in the mammalian immune system. Expression from the gene is tightly regulated with no detectable expression in resting T cells and a strong induction following T cell activation. The IL-2 proximal promoter (+1 to -300) contains many well-defined transcriptional activation elements that respond to T cell stimulation. To determine the role of chromatin structure in the regulation of interleukin-2 gene transcription, nucleosome assembly across the IL-2 promoter region was examined using in vitro chromatin reconstitution assays. The IL-2 promoter assembles a nucleosome that is both translationally and rotationally positioned, spanning some of the major functional control elements. The binding of transcription factors to these elements, with the exception of the architectural protein HMGA1, was occluded by the presence of the nucleosome. Analysis of the chromatin architecture of the IL-2 gene in Jurkat T cells provided evidence for the presence of a similarly positioned nucleosome in vivo. The region encompassed by this nucleosome becomes remodeled following activation of Jurkat T cells. These observations suggest that the presence of a positioned nucleosome across the IL-2 proximal promoter may play an important role in maintaining an inactive gene in resting T cells and that remodeling of this nucleosome is important for gene activation.