Gégonne A, Bosselut R, Bailly R A, Ghysdael J
CNRS-URA 1443, Institut Curie, Section de Biologie, Orsay, France.
EMBO J. 1993 Mar;12(3):1169-78. doi: 10.1002/j.1460-2075.1993.tb05758.x.
Ets1 is the prototype of a family of transcriptional activators whose activity depends on the binding to specific DNA sequences characterized by an invariant GGA core sequence. We have previously demonstrated that transcriptional activation by Ets1 of the long terminal repeat (LTR) of human T cell lymphotropic virus type 1 is strictly dependent on the binding of Ets1 to two sites, ERE-A and ERE-B, localized in a 44 bp long Ets-responsive region (ERR1). We report here that the activity of ERR1 as an efficient Ets1 response element in HeLa cells also depends on the integrity of an Sp1 binding site localized immediately upstream of ERE-A. The response to Ets1 of an element restricted to the SP1/ERE-A binding sites is also strictly dependent on both the Ets1 and Sp1 binding sites. In vitro, Sp1 and Ets1 are shown to cooperate to form a ternary complex with the SP1/ERE-A element. Reconstitution experiments in Drosophila melanogaster Schneider cells show that Ets1 and Sp1 act synergistically to activate transcription from either the ERR1 or the SP1/ERE-A elements and that synergy requires the binding of both Sp1 and Ets1 to their cognate sites. SP1/ERE-A elements are found in the enhancer/promoter region of several cellular genes, suggesting that synergy between Ets1 and Sp1 is not restricted to the ERR1 region of the HTLV1 LTR. These results strengthen the notion that Ets1 as well as other members of the Ets family usually function as components of larger transcription complexes to regulate the activity of a variety of viral and cellular genes.
Ets1是转录激活因子家族的原型,其活性取决于与特定DNA序列的结合,这些序列的特征是具有不变的GGA核心序列。我们之前已经证明,Ets1对人1型嗜T细胞病毒长末端重复序列(LTR)的转录激活严格依赖于Ets1与位于44 bp长的Ets反应区域(ERR1)中的两个位点ERE-A和ERE-B的结合。我们在此报告,ERR1作为HeLa细胞中有效的Ets1反应元件的活性也取决于位于ERE-A上游紧邻位置的Sp1结合位点的完整性。仅包含SP1/ERE-A结合位点的元件对Ets1的反应也严格依赖于Ets1和Sp1结合位点。在体外,Sp1和Ets1显示出协同作用,与SP1/ERE-A元件形成三元复合物。在黑腹果蝇Schneider细胞中的重组实验表明,Ets1和Sp1协同作用以激活来自ERR1或SP1/ERE-A元件的转录,并且协同作用需要Sp1和Ets1都与其同源位点结合。在几个细胞基因的增强子/启动子区域中发现了SP1/ERE-A元件,这表明Ets1和Sp1之间的协同作用并不局限于HTLV1 LTR的ERR1区域。这些结果强化了这样一种观念,即Ets1以及Ets家族的其他成员通常作为更大转录复合物的组成部分发挥作用,以调节多种病毒和细胞基因的活性。