REGULATION OF THE TRANSFORMING GROWTH-FACTOR-BETA-1 AND FACTOR-BETA-3 PROMOTERS BY TRANSCRIPTION FACTOR SP1
REGULATION OF THE TRANSFORMING GROWTH-FACTOR-BETA-1 AND FACTOR-BETA-3 PROMOTERS BY TRANSCRIPTION FACTOR SP1
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DOI：
10.1016/0378-1119(93)90272-5
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发表时间：
1993-07-30
期刊：
影响因子：
3.5
通讯作者：
SPORN, MB
中科院分区：
文献类型：
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作者：
GEISER, AG;BUSAM, KJ;SPORN, MB
编码三种哺乳动物转化生长因子- β （tgf - β 1、- β 2和- β 3）的基因启动子区域在序列上几乎没有相似性，这表明转录控制存在差异。为了进一步了解单个tgf - β基因的转录调控，我们测试了三个tgf - β启动子区域（ptgf - β）的转录因子Sp1的刺激，并通过ptgf - β a1和ptgf - β a3的序列分析确定了几个可能的spl结合位点。采用果蝇细胞培养系统检测ptgf - β::cat构建体在缺乏Sp1同源物的细胞背景下与Sp1表达质粒共表达的表达水平。Sp1强烈刺激pTGF-beta1和pTGF-beta3，而pTGF-beta2完全不受影响。tgf - β 1和tgf - β 3基因的启动子片段，而不是tgf - β 2，能够竞争Sp1与含有一致Sp1结合位点的DNA低聚物的结合。此外，使用纯Sp1或核蛋白提取物可观察到与pTGF-beta1和pTGF-beta3片段的特异性结合。因此，TGF-beta1和TGF-beta3（而不是TGF-beta2）受到转录因子Sp1的调控，表明其蛋白产物在功能上非常相似的基因的差异转录调控。
The promoter regions of the genes encoding the three mammalian transforming growth factors-beta (TGF-beta1, -beta2, and -beta3) show little similarity in sequence, suggesting diverse transcriptional control. As a step towards understanding transcriptional regulation of the individual TGF-beta genes we tested each of the three TGF-beta promoter regions (pTGF-beta) for stimulation by the transcription factor Sp1, given that several possible Spl-binding sites were identified by sequence analysis in pTGF-beta1 and pTGF-beta3. A Drosophila melanogaster cell culture system was employed to examine expression levels of pTGF-beta::cat constructs coexpressed with an Sp1 expression plasmid in a cell background devoid of any Sp1 homolog. While both pTGF-beta1 and pTGF-beta3 were strongly stimulated by Sp1, pTGF-beta2 was completely unaffected. Promoter fragments of the TGF-beta1 and TGF-beta3 genes, but not TGF-beta2 were able to compete for binding of Sp1 to DNA oligomers containing consensus Sp1-binding sites. Moreover, specific binding to pTGF-beta1 and pTGF-beta3 fragments was seen using pure Sp1 or nuclear protein extracts. Thus, TGF-beta1 and TGF-beta3 (but not TGF-beta2) are regulated by the transcription factor Sp1, indicating differential transcriptional regulation of genes whose protein products are functionally very similar.