Müeller-Storm H P, Sogo J M, Schaffner W
Institut für Molekularbiologie II der Universität Zürich, Switzerland.
Cell. 1989 Aug 25;58(4):767-77. doi: 10.1016/0092-8674(89)90110-4.
Two principal models have been invoked to explain transcriptional stimulation of RNA polymerase II genes by enhancers/upstream promoter elements: in one, upstream regulatory sequences directly interact with proximal promoter elements via proteins bound to the DNA ("looping" model); in the other, RNA polymerase II (or a transcription factor) binds to distal sequences and then scans along the DNA until it reaches the promoter ("scanning" or "entry site" model). So far, it has been reported that enhancers or upstream promoter elements transmit their effect on a gene only via covalently closed DNA, i.e., in a cis configuration. The looping model predicts, however, that the effect can be transmitted also in certain trans configurations. Here we demonstrate that an enhancer from SV40 or cytomegalovirus can stimulate transcription in vitro even when noncovalently attached to the beta-globin promoter via the proteins streptavidin or avidin. These findings are consistent with the looping model rather than the scanning model. In addition, stimulation of transcription in trans, as shown by our experiments, may be found in nature in phenomena such as transvection, where one chromosome affects gene expression in the paired homolog.
为了解释增强子/上游启动子元件对RNA聚合酶II基因的转录刺激作用，人们提出了两种主要模型：一种是上游调控序列通过与DNA结合的蛋白质直接与近端启动子元件相互作用（“环化”模型）；另一种是RNA聚合酶II（或转录因子）结合到远端序列，然后沿DNA扫描，直到到达启动子（“扫描”或“进入位点”模型）。到目前为止，已有报道称增强子或上游启动子元件仅通过共价闭合的DNA（即顺式构型）对基因发挥作用。然而，环化模型预测，这种作用在某些反式构型中也可以传递。在此我们证明，即使通过链霉亲和素或抗生物素蛋白与β-珠蛋白启动子非共价连接，SV40或巨细胞病毒的增强子也能在体外刺激转录。这些发现与环化模型而非扫描模型一致。此外，正如我们的实验所示，反式转录刺激在诸如异位效应（一条染色体影响配对同源染色体上的基因表达）等自然现象中可能存在。
