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首页> 外文期刊>Genomics >The Bax inhibitor-1 gene is differentially regulated in adult testis and developing lung by two alternative TATA-less promoters.
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The Bax inhibitor-1 gene is differentially regulated in adult testis and developing lung by two alternative TATA-less promoters.

机译：在成人的睾丸和发育中的肺中，Bax inhibitor-1基因受到两个非TATA启动子的差异调节。

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摘要

We identified Bax inhibitor-1, BI-1, as a developmentally regulated gene product in perinatal lung using suppressive subtractive hybridization. BI-1 is a novel suppressor of apoptosis that was previously cloned as testis-enhanced gene transcript (TEGT). However, sequence analysis of lung BI-1 revealed unique nucleotides starting 29 bases upstream of the ATG initiation codon and extending to the 5' end of lung-derived BI-1 cDNA compared to the original transcript from the testis. Cloning and sequencing of the upstream region of the BI-1 gene revealed that these unique sequences originated from two alternative first exons, located in tandem and separated by approximately 600 bases. Neither was preceded by a TATA box in the usual position, and S1 nuclease mapping at each exon 1 revealed multiple transcription start points with a major site being overlapped by a consensus initiator element. Promoter activity from each region was documented by transient transfection analysis in vitro using DNA sequences ligated to a reporter gene. The proximal promoter, P1, may exhibit cell type-specific differences in fibroblasts versus epithelia, whereas the distal promoter, P2, may exhibit species-specific differences in rat versus human cells. RT-PCR analysis for expression in adult tissues using exon 1-specific 5' primers and common 3' primers revealed that P1 is tissue-specific; P2 is ubiquitously active. The developmental regulation of BI-1 in the late fetal and early postnatal lung is specific for P2, indicating that these two TATA-less promoters are differentially regulated in adult testis and developing lung. Since Bax inhibitor-1 functions as a suppressor of apoptosis, its expression could provide a survival advantage for select cell populations during the peak period of apoptosis that occurs at birth. Copyright 1999 Academic Press.
机译：我们使用抑制性消减杂交鉴定了Bax抑制剂-1，BI-1，作为围产期肺中发育受调控的基因产物。 BI-1是一种新型的凋亡抑制因子，先前已被克隆为睾丸增强基因转录本（TEGT）。但是，肺BI-1的序列分析显示，与来自睾丸的原始转录本相比，独特的核苷酸起始于ATG起始密码子上游29个碱基，并延伸至肺源BI-1 cDNA的5'端。 BI-1基因上游区域的克隆和测序表明，这些独特的序列源自两个可替代的第一个外显子，串联排列并相隔约600个碱基。两者均未在通常位置的TATA框之前加上，并且每个外显子1上的S1核酸酶作图都揭示了多个转录起始点，主要位点被共有启动子元件重叠。通过使用连接至报告基因的DNA序列进行体外瞬时转染分析，记录了每个区域的启动子活性。近端启动子P1在成纤维细胞与上皮细胞中可能表现出细胞类型特异性差异，而远端启动子P2在大鼠与人类细胞中可能表现出物种特异性差异。使用外显子1特异性5'引物和常见3'引物进行的RT-PCR分析在成人组织中的表达表明，P1是组织特异性的。 P2无处不在。胎儿晚期和产后早期肺中BI-1的发育调控对P2具有特异性，表明这两个TATA-less启动子在成年睾丸和发育中的肺中受到不同的调控。由于Bax抑制剂1起到凋亡抑制作用，因此其表达可以为出生时发生的凋亡高峰期的特定细胞群提供生存优势。版权所有1999 Academic Press。

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