Structure of the human Bim gene and its transcriptional regulation in Baf-3, interleukin-3-dependent hematopoietic cells
Structure of the human Bim gene and its transcriptional regulation in Baf-3, interleukin-3-dependent hematopoietic cells
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DOI：
10.1007/s11033-004-7656-0
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发表时间：
2005-06
影响因子：
2.8
通讯作者：
H. Matsui;T. Shinjyo;T. Inaba
中科院分区：
文献类型：
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作者：
H. Matsui;T. Shinjyo;T. Inaba
细胞因子剥夺诱导细胞周期阻滞和细胞因子依赖性造血祖细胞凋亡。先前的研究表明，在依赖白细胞介素(IL)-3的Baf-3细胞中，凋亡主要是由bim引起的，bim是一种仅限bh3的细胞死亡激活剂，属于Bcl-2超家族。由于bimmrna是由IL-3饥饿诱导的，我们假设来自IL-3受体的信号可能通过其转录水平调节bimmrna的表达。在这里，我们确定了bimgene的转录起始位点和三个候选的远程增强/沉默区域。我们发现基因上游起始位点的区域表现出很强的启动子活性，并且在第一个内含子内存在负调控区域。然而，这些转录调控元件都不依赖于il -3。此外，核径流分析显示，在没有或存在IL-3的情况下，转录起始率相似。虽然其他研究已经证实了bimby神经生长因子（NGF）在神经分化的PC12嗜铬细胞瘤细胞中的转录调控，但这不太可能是IL-3下调bimin Baf-3细胞表达的机制。
Deprivation of cytokines induces cell cycle arrest and apoptosis in cytokine-dependent hematopoietic progenitors. Previous studies have indicated that in Baf-3, interleukin (IL)-3-dependent cells, apoptosis is caused predominantly byBim, a BH3-only cell death activator that belongs to the Bcl-2 superfamily. BecauseBimmRNA is induced by IL-3 starvation, we hypothesized that signals originating from the IL-3 receptor might regulate the expression ofBimat the level of its transcription. Here, we identified the transcriptional initiation site and three candidate remote enhancer/silencer regions of theBimgene. We show that the region of the gene upstream of the initiation site exhibits strong promoter activity and that there are negative regulatory regions within the first intron. However, none of these transcriptional regulatory elements was IL-3-dependent. In addition, a nuclear run-off assay revealed a similar rate of transcription initiation in the absence or presence of IL-3. Although others have demonstrated the transcriptional regulation ofBimby nerve growth factor (NGF) in neuronally differentiated PC12 pheochromocytoma cells, this is unlikely to be the mechanism through which IL-3 downregulates the expression ofBimin Baf-3 cells.