Transcription of the Interleukin-1 Receptor-related T1 Gene Is Initiated at Different Promoters in Mast Cells and Fibroblasts (*)
Transcription of the Interleukin-1 Receptor-related T1 Gene Is Initiated at Different Promoters in Mast Cells and Fibroblasts (*)
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DOI：
10.1074/jbc.271.1.124
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发表时间：
1996-01
期刊：
影响因子：
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通讯作者：
T. Gächter;A. Werenskiold;R. Klemenz
中科院分区：
文献类型：
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作者：
T. Gächter;A. Werenskiold;R. Klemenz
延迟早期血清反应基因T1编码免疫球蛋白超家族的糖蛋白，与1型白细胞介素-1受体具有显著的序列相似性。T1基因在成纤维细胞中被转录成丰富的2.7-kb和罕见的5-kb mRNA，以响应增殖诱导刺激。它主要在成年小鼠的骨髓和培养的肥大细胞中产生较长的转录本。选择性3′加工负责这两种mRNA形式。短转录本编码与白细胞介素-1受体的胞外结构域具有显著相似性的分泌蛋白，而长mRNA被翻译成具有额外推定的跨膜和胞内结构域的蛋白。在这里，我们表明，T1在肥大细胞和成纤维细胞的转录起始于两个不同的起始位点，这是10.5 kb的距离。选择性第一外显子都剪接到含有翻译起始位点的外显子2。北方印迹分析和引物延伸实验表明，启动子的使用是严格的细胞类型特异性。肥大细胞中的T1转录仅在远端启动子处启动，而成纤维细胞中的短和长T1 mRNA均在近端启动子处启动。在肥大细胞特异性远端外显子1的5′侧翼区鉴定出两个加塔-1元件。
The delayed early serum response gene T1 encodes glycoproteins of the immunoglobulin superfamily with significant sequence similarity to the type 1 interleukin-1 receptor. The T1 gene is transcribed in fibroblasts into an abundant 2.7-kilobase (kb) and a rare 5-kb mRNA in response to proliferation-inducing stimuli. It gives predominantly rise to the longer transcript in the bone marrow of adult mice and in cultured mast cells. Alternative 3′ processing is responsible for the two mRNA forms. The short transcript encodes a secreted protein with marked similarity to the extracellular domain of the interleukin-1 receptor, whereas the long mRNA is translated into a protein with an additional putative transmembrane and an intracellular domain. Here we demonstrate that T1 transcription in mast cells and fibroblasts initiates at two different start sites which are 10.5 kb apart. The alternative first exons are both spliced to exon 2 which contains the translation start site. Northern blot analysis and primer extension experiments revealed that promoter usage is strictly cell type-specific. T1 transcription in mast cells is initiated exclusively at the distal promoter, whereas in fibroblasts both the short and the long T1 mRNA start at the proximal promoter. Two GATA-1 elements were identified in the 5′-flanking region of the mast cell-specific distal exon 1.