Cooperation of GATA-1 and Sp1 can result in synergistic transcriptional activation or interference.
Cooperation of GATA-1 and Sp1 can result in synergistic transcriptional activation or interference.
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GATA-1 和 Sp1 的合作可以导致协同转录激活或干扰。
DOI：
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发表时间：
1993
影响因子：
4.8
通讯作者：
J. Nowock
中科院分区：
文献类型：
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作者：
K. Fischer;A. Haese;J. Nowock
加塔-1是一种谱系限制性转录因子。事实上，所有红细胞表达的基因在其调控元件中都含有加塔识别位点。共转染/反式激活试验表明，尽管加塔-1作为唯一的细胞限制性转录因子足以激活某些红系特异性启动子，但并非所有这些启动子都有反应，这表明需要与其他因子合作。为了研究加塔-1与其他反式激活因子的相互作用，我们通过体外转录和转染到红系K562细胞或异源果蝇SL 2细胞中来分析作为应答系统的人γ-珠蛋白启动子的序列基序。单独的加塔-1不能激活启动子。然而，加塔-1发挥的作用与普遍存在的反式激活因子Sp1一致。根据因子浓度和同源结合位点的序列背景，这种相互作用可能导致协同转录激活或干扰。在体外实验中，加塔-1和Sp1在DNA结合中没有协同作用。这表明功能合作是由蛋白质与传递激活信号的其他因子相互作用介导的。Sp1结合的CCACCC基序被认为是γ-珠蛋白启动子高活性的关键。该位点与NFI/CTF家族成员的识别序列重叠。NFI没有反式激活，但它干扰Sp1介导的刺激，因此与Sp1/加塔-1合作。这些数据，再加上系统发育的证据，表明CCACCC区域很可能代表一个调节开关元件。
GATA-1 is a lineage-restricted transcription factor. Virtually all erythroid-expressed genes contain GATA recognition sites in their regulatory elements. Cotransfection/transactivation assays have revealed that, although GATA-1 as the only cell-restricted transcription factor is sufficient to activate some of the erythroid-specific promoters, not all such promoters are responsive, suggesting a requirement for cooperation with other factors. To study the interaction of GATA-1 with other transactivators, we analyzed sequence motifs of the human gamma-globin promoter as response system by in vitro transcription and by transfections into erythroid K562 cells or into heterologous Drosophila SL2 cells. GATA-1 alone did not activate the promoter. However, GATA-1 exerted an effect in concert with the ubiquitous transactivator Sp1. Depending on the factor concentrations and the sequence context of the cognate binding sites, this interaction could result in synergistic transcriptional activation or in interference. GATA-1 and Sp1 did not cooperate in DNA binding when tested in vitro. This suggests that the functional cooperation is mediated by protein interactions with additional factor(s) which transmit the activator signal. The Sp1-binding CCACCC motif was found to be critical for high activity of the gamma-globin promoter. This site overlaps with a recognition sequence for members of the NFI/CTF family. NFI did not transactivate, but it interfered with Sp1-mediated stimulation and hence with Sp1/GATA-1 cooperation. These data, together with phylogenetic evidence, suggest that the CCACCC region is likely to represent a regulatory switch element.