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首页> 外文期刊>Molecular and Cellular Biology >Characterization of the mouse transforming growth factor-beta 1 promoter and activation by the Ha-ras oncogene.
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Characterization of the mouse transforming growth factor-beta 1 promoter and activation by the Ha-ras oncogene.

机译：小鼠转化生长因子-beta 1启动子的表征和Ha-ras癌基因的激活。

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We have cloned and sequenced a mouse genomic transforming growth factor beta 1 (TGF-beta 1) DNA fragment that includes the 5' untranslated and regulatory regions of the gene. High-sequence homology with the human TGF-beta 1 gene (66% nucleotide identity in 2.7 kb of DNA upstream of the translational start site) suggested evolutionary conservation of transcriptional regulation for TGF-beta 1. The absence of TATA or CAAT box sequences but the presence of several Sp1-binding and AP-2-like sequences in the promoter region was noted, as previously reported for the human gene. Two transcriptional initiation sites separated by 290 bp were identified by S1 nuclease analysis; these corresponded to transcripts with 866 and 576 nucleotides of 5' untranslated leader sequence. S1 analysis of different mouse tissues indicated that the two transcripts were present in the same ratio even though the total level of TGF-beta 1 mRNA transcripts varied between tissues. Promoter activity adjacent to both transcriptional start sites was demonstrated by using chloramphenicol acetyltransferase fusion genes assayed in mouse AKR-2B fibroblast cells. Transcriptional activation of the promoter by the Ha-ras oncogene was also demonstrated. The minimal promoter constructs (113 and 104 bp 5' of the first and second transcriptional start sites, respectively) were sufficient for induction by Ha-ras. These studies characterize the 5' structure and basal promoter activity of the mouse TGF-beta 1 gene as well as the transcriptional activation of TGF-beta 1 by the Ha-ras oncogene.
机译：我们已经克隆并测序了小鼠基因组转化生长因子β1（TGF-β1）DNA片段，其中包括该基因的5'非翻译和调节区。与人类TGF-β1基因的高度同源性（翻译起始位点上游2.7 kb DNA中66％的核苷酸同一性）表明TGF-β1转录调控的进化保守性。没有TATA或CAAT盒序列，但是如先前关于人类基因的报道，注意到在启动子区域中存在几个Sp1-结合和AP-2-样序列。通过S1核酸酶分析鉴定了两个相距290 bp的转录起始位点;这些对应于具有5'非翻译前导序列的866和576个核苷酸的转录物。对不同小鼠组织的S1分析表明，即使TGF-β1mRNA转录本的总水平在组织之间有所不同，两种转录本也以相同的比例存在。通过使用在小鼠AKR-2B成纤维细胞中测定的氯霉素乙酰基转移酶融合基因，证明了与两个转录起始位点相邻的启动子活性。还证实了Ha-ras癌基因对启动子的转录激活。最小的启动子构建体（第一和第二转录起始位点分别为113和104 bp 5'）足以被Ha-ras诱导。这些研究表征了小鼠TGF-β1基因的5'结构和基础启动子活性，以及​​Ha-ras癌基因对TGF-β1的转录激活。

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