Characterization of the entire transcription unit of the mouse fibroblast growth factor 1 (FGF-1) gene - Tissue-specific expression of the FGF-1.A mRNA
Characterization of the entire transcription unit of the mouse fibroblast growth factor 1 (FGF-1) gene - Tissue-specific expression of the FGF-1.A mRNA
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DOI：
10.1074/jbc.274.17.11937
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发表时间：
1999-04-23
影响因子：
4.8
通讯作者：
Chiu, IM
中科院分区：
文献类型：
--
作者：
Madiai, F;Hackshaw, KV;Chiu, IM
成纤维细胞生长因子-1，又称酸性成纤维细胞生长因子，是多种中胚层和神经外胚层来源的细胞的有丝分裂原，也是体内的血管生成因子。它与动脉粥样硬化、癌症和炎症性疾病等血管生成疾病有关。在本研究中，描述了小鼠成纤维细胞生长因子-1基因的完整转录单位，包括四个启动子。通过核苷酸序列和核糖核酸酶保护分析，我们确定其3‘端位于终止密码子下游的3.2kb碱基对。我们之前已经克隆并鉴定了人类1B启动子的小鼠同源基因，以及一个新的上游未翻译的外显子。为了阐明成纤维细胞生长因子-I基因表达的调控机制，从P1文库中分离并鉴定了含有TATA和CAAT共同序列(成纤维细胞生长因子-1.A)的小鼠启动子。我们进一步确定，小鼠心脏是成纤维细胞生长因子-1的最丰富来源。最后，通过核糖核酸酶保护分析和5‘-末端快速扩增，我们确定了成纤维细胞生长因子-1的转录起始点。
Fibroblast growth factor 1 (FGF-1, also known as acidic FGF) is a mitogen for a variety of mesoderm- and neuroectoderm-derived cells, as well as an angiogenic factor in vivo. It has been implicated in angiogenic diseases including atherosclerosis, cancer and inflammatory diseases. In the present study, the entire transcriptional unit of the mouse FGF-1 gene, including four promoters, is characterized. By nucleotide sequence and RNase protection analyses, we have determined that its 3'-end resides 3.2 kilobase pairs downstream from the stop codon. We have previously cloned and characterized the mouse homologue of the human 1B promoter, as well as a novel upstream untranslated exon. In order to elucidate the regulatory mechanism of FGF-I gene expression, the mouse promoter containing TATA and CAAT consensus sequences (FGF-1.A) was isolated from a P1 library and characterized. We further determined that the mouse heart is the most abundant source for the FGF-1.A mRNA. Finally, via both RNase protection analysis and 5'-rapid amplification of cDNA ends, we determined the transcription start site of the FGF-1.A mRNA.