MAST CELL SPECIFIC REGULATION OF IL4 GENE EXPRESSION

描述：（改编自申请人摘要）白细胞介素-4（IL-4） 是一种重要的免疫调节细胞因子，对免疫功能具有多种作用 系统成熟和功能。 已知两种主要的细胞类型产生 IL-4、T细胞和肥大细胞。 IL-4基因表达的调控 这些细胞类型已被证明是不同的，并且是调节细胞的调节元件。 该基因的第二个内含子是肥大细胞特异性的，有助于肥大细胞的增殖。 这两种细胞类型的调节机制不同。 这个项目是 基于肥大细胞表达截短的IL-4 mRNA的报道， 仅包含外显子3和4。 这种截短的mRNA只能通过 RNA酶保护试验，因为北方印迹分析不足以 灵敏地区分截短的mRNA和全长mRNA。 内含子DNA的分析揭示了一个“TATA-少”启动子的存在 元件，这表明这种截短的mRNA的转录可能启动 在这个内含子调控元件中。 该项目的重点是进一步 描述这个截短的转录本， 其表达的生物学后果。 其目的是：（1）评估 截短转录本的表达谱; 2）评估 转录本和3）确定内含子内的调控元件 调节截短的mRNA的转录。 因为有可能 这种新的转录本可能代表了一种重要的调节机制， IL-4基因表达及其背后的机制 表达，并通过其调节IL-4的生物学活性。

DESCRIPTION: (Adapted from the applicant's abstract) Interleukin-4 (IL-4) is an important immunoregulatory cytokine with diverse effects on immune system maturation and function. Two major cell types are known to produce IL-4, T cells and mast cells. The regulation of IL-4 gene expression in these cell types has been shown to be different and a regulatory element in the second intron of the gene is mast cell specific, contributing to the different mechanisms of regulation in the two cell types. This project is based on a report that mast cells express a truncated IL-4 mRNA, encompassing only exons 3 and 4. This truncated mRNA was only detected by RNAse protection assays as Northern blot analysis was not sufficiently sensitive to distinguish the truncated mRNA from the full length mRNA. Analysis of intronic DNA has revealed the presence of a "TATA-less" promoter elements, suggesting that transcription of this truncated mRNA may initiate in this intronic regulatory element. This project is focused on further characterizing this truncated transcript and assessing the possible biological consequences of its expression. The aims are: 1) to assess the expression profile of the truncated transcript; 2) to assess the function of the transcript and 3) to define the regulatory elements within the intron that regulate transcription of the truncated mRNA. As it is possible that this novel transcript may represent an important mechanism for regulating IL-4 gene expression and for understanding the mechanisms behind its expression and by which it may regulate IL-4 biological activity.