Sp3 and Sp4 can repress transcription by competing with Sp1 for the core cis-elements on the human ADH5/FDH minimal promoter
Sp3 and Sp4 can repress transcription by competing with Sp1 for the core cis-elements on the human ADH5/FDH minimal promoter
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DOI：
10.1074/jbc.274.1.20
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发表时间：
1999-01-01
影响因子：
4.8
通讯作者：
Hur, MW
中科院分区：
文献类型：
--
作者：
Kwon, HS;Kim, MS;Hur, MW
人类乙醇脱氢酶5基因（也称为甲醛脱氢酶基因，ADH 5/FDH）具有富含CC的启动子，该启动子具有许多转录因子结合的位点。从-34个碱基对（bp）延伸至+61 bp的最小启动子指导在几种不同细胞中的高水平转录，这与基因的普遍表达一致。我们分析了Spl多基因家族成员对ADH 5/FDH的转录调控。两个核心顺式元件（-22 bp到+22 bp）对Spl的亲和力最高，突变显示这些顺式元件对转录激活至关重要。Sp3和Sp 4的锌指结构域也选择性地结合核心顺式元件。在缺乏内源性Spl的果蝇SL 2细胞中，最小启动子不能驱动转录。Spl的引入激活转录超过50倍，表明Spl在转录起始中是关键的。Sp3和Sp 4均不能激活ADH 5/FDH基因的转录，而Sp1的转录激活作用被Sp3和Sp 4所抑制。这些结果表明，Sp3和Sp 4可以通过与Sp1竞争与核心顺式元件的结合来抑制转录，不同细胞中Sp1、Sp3和Sp 4的含量可能是调控ADH 5/FDH基因转录的关键因素。
The human alcohol dehydrogenase 5 gene (also known as the formaldehyde dehydrogenase gene, ADH5/FDH) has a CC-rich promoter with many sites at which transcription factors bind. A minimal promoter extending from -34 base pairs (bp) to +61 bp directs high levels of transcription in several different cells, consistent with the ubiquitous expression of the gene. Nearly the entire minimal promoter can be bound by Spl, We analyzed the transcriptional regulation of ADH5/FDH by members of the Spl multigene family. Two core cis-elements (-22 bp to +22 bp) had the highest affinity for Spl, Mutagenesis revealed that these cis-elements are critical for transcriptional activation. The zinc-finger domains of Sp3 and Sp4 also bind selectively to the core cis-elements. In Drosophila SL2 cells, which lack endogenous Spl, the minimal promoter cannot drive transcription. Introduction of Spl activated transcription over 50-fold, suggesting that Spl is critical in the initiation of transcription. Neither Sp3 nor Sp4 was able to activate transcription in those cells, and transcriptional activation by Spl was repressed by Sp3 or Sp4, These data suggest that Sp3 and Sp4 can repress transcription by competing with Spl for binding to the core cis-elements, The content of Spl, Sp3, and Sp4 in different cells may be critical factors regulating transcription of the ADH5/FDH gene.