Activation of the granulocyte-macrophage colony-stimulating factor promoter in T cells requires cooperative binding of Elf-1 and AP-1 transcription factors.
Activation of the granulocyte-macrophage colony-stimulating factor promoter in T cells requires cooperative binding of Elf-1 and AP-1 transcription factors.
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T 细胞中粒细胞-巨噬细胞集落刺激因子启动子的激活需要 Elf-1 和 AP-1 转录因子的协同结合。
DOI：
10.1128/mcb.14.2.1153-1159.1994
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发表时间：
1994
影响因子：
5.3
通讯作者：
Leiden,JM
中科院分区：
文献类型：
--
作者：
Wang,CY;Bassuk,AG;Boise,LH;Thompson,CB;Bravo,R;Leiden,JM
粒细胞-巨噬细胞集落刺激因子（GM-CSF）基因作为T淋巴细胞活化过程中转录诱导的模型系统已被广泛研究。GM-CSF基因在静息的外周血T细胞中不表达，但在通过细胞表面T细胞受体活化后在转录水平上被快速诱导。位于人GM-CSF TATA盒（bp-34至-52）的5′端的高度保守的19-bp元件，本文称为嘌呤盒1（PB 1），已显示结合T细胞核蛋白复合物，并且是T细胞活化后GM-CSF基因的转录诱导所需的。PB 1序列基序在人和鼠GM-CSF基因中高度保守。在这份报告中，我们证明，PB 1元件单独赋予诱导后，转染到人Jurkat T细胞的异源启动子。此外，我们确定了一个主要的PB 1核蛋白结合复合物，不存在于静息外周血T细胞，但T细胞活化后迅速诱导。序列分析表明，PB 1由Ets和AP-1转录因子的相邻结合位点组成。体外诱变实验表明，Ets和AP-1位点都是诱导型PB 1核蛋白复合物结合以及该元件和活化T细胞中GM-CSF启动子的转录活性所需的。使用不同的Ets和AP-1家族成员的特异性抗体，我们证明了主要的诱导PB 1结合活性存在于活化的T细胞核提取物是由Elf-1，c-Fos，和JunB转录因子。两者合计，这些结果表明，特定的Ets和AP-1家族成员之间的合作相互作用是重要的，在调节诱导型基因的表达后，T细胞活化。
The granulocyte-macrophage colony-stimulating factor (GM-CSF) gene has been studied extensively as a model system of transcriptional induction during T-lymphocyte activation. The GM-CSF gene is not expressed in resting peripheral blood T cells but is rapidly induced at the transcriptional level following activation through the cell surface T-cell receptor. A highly conserved 19-bp element located immediately 5′ of the human GM-CSF TATA box (bp -34 to -52), herein called purine box 1 (PB1), has been shown to bind a T-cell nuclear protein complex and to be required for transcriptional induction of the GM-CSF gene following T-cell activation. The PB1 sequence motif is highly conserved in both human and murine GM-CSF genes. In this report, we demonstrate that the PB1 element alone confers inducibility on a heterologous promoter following transfection into human Jurkat T cells. In addition, we identify a major PB1 nuclear protein-binding complex that is not present in resting peripheral blood T cells but is rapidly induced following T-cell activation. Sequence analysis revealed that PB1 is composed of adjacent binding sites for Ets and AP-1 transcription factors. In vitro mutagenesis experiments demonstrated that both the Ets and AP-1 sites are required for binding of the inducible PB1 nuclear protein complex and for the transcriptional activity of this element and the GM-CSF promoter in activated T cells. Using antibodies specific for different Ets and AP-1 family members, we demonstrate that the major inducible PB1-binding activity present in activated T-cell nuclear extracts is composed of the Elf-1, c-Fos, and JunB transcription factors. Taken together, these results suggest that cooperative interactions between specific Ets and AP-1 family members are important in regulating inducible gene expression following T-cell activation.