Frain M, Hardon E, Ciliberto G, Sala-Trepat J M
European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Mol Cell Biol. 1990 Mar;10(3):991-9. doi: 10.1128/mcb.10.3.991-999.1990.
A segment of 1,022 base pairs (bp) of the 5'-flanking region of the human albumin gene, fused to a reporter gene, directs hepatoma-specific transcription. Three functionally distinct regions have been defined by deletion analysis: (i) a negative element located between bp -673 and -486, (ii) an enhancer essential for efficient albumin transcription located between bp -486 and -221, and (iii) a promoter spanning a region highly conserved throughout evolution. Protein-binding studies have demonstrated that a liver trans-acting factor which interacts with the enhancer region is the well-characterized transcription factor LF-B1, which binds to promoters of several liver-specific genes. A synthetic oligodeoxynucleotide containing the LF-B1-binding site is sufficient to act as a tissue-specific transcriptional enhancer when placed in front of the albumin promoter. The fact that the same binding site functions in both an enhancer and a promoter suggests that these two elements influence the initiation of transcription through similar mechanisms.
人类白蛋白基因5'侧翼区的一段1022个碱基对(bp),与一个报告基因融合后,可指导肝癌特异性转录。通过缺失分析确定了三个功能不同的区域:(i)位于bp -673和-486之间的一个负性元件;(ii)位于bp -486和-221之间的对高效白蛋白转录必不可少的一个增强子;(iii)一个跨越整个进化过程中高度保守区域的启动子。蛋白质结合研究表明,与增强子区域相互作用的一种肝脏反式作用因子是特征明确的转录因子LF-B1,它可结合几个肝脏特异性基因的启动子。当置于白蛋白启动子之前时,一个含有LF-B1结合位点的合成寡脱氧核苷酸足以充当组织特异性转录增强子。同一结合位点在增强子和启动子中均起作用这一事实表明,这两个元件通过相似的机制影响转录起始。