Dang W, Sun X H, Sen R
Department of Biology, Brandeis University, Waltham, Massachusetts 02254-9110, USA.
Mol Cell Biol. 1998 Mar;18(3):1477-88. doi: 10.1128/MCB.18.3.1477.
The muE motifs of the immunoglobulin mu heavy-chain gene enhancer bind ubiquitously expressed proteins of the basic helix-loop-helix (bHLH) family. These elements work together with other, more tissue-restricted elements to produce B-cell-specific enhancer activity by presently undefined combinatorial mechanisms. We found that muE2 contributed to transcription activation in B cells only when the muE3 site was intact, providing the first evidence for functional interactions between bHLH proteins. In vitro assays showed that bHLH zipper proteins binding to muE3 enhanced Ets-1 binding to muA. One of the consequences of this protein-protein interaction was to facilitate binding of a second bHLH protein, E47, to the muE2 site, thereby generating a three-protein-DNA complex. Furthermore, transcriptional synergy between bHLH and bHLH zipper factors also required an intermediate ETS protein, which may bridge the transcription activation domains of the bHLH factors. Our observations define an unusual form of cooperation between bHLH and ETS proteins and suggest mechanisms by which tissue-restricted and ubiquitous factors combine to generate tissue-specific enhancer activity.
免疫球蛋白μ重链基因增强子的μE基序结合基本螺旋-环-螺旋（bHLH）家族中普遍表达的蛋白质。这些元件与其他更多组织限制性元件共同作用，通过目前尚未明确的组合机制产生B细胞特异性增强子活性。我们发现，只有当μE3位点完整时，μE2才有助于B细胞中的转录激活，这为bHLH蛋白之间的功能相互作用提供了首个证据。体外实验表明，与μE3结合的bHLH拉链蛋白增强了Ets-1与μA的结合。这种蛋白质-蛋白质相互作用的一个结果是促进了另一种bHLH蛋白E47与μE2位点的结合，从而形成了一种三蛋白-DNA复合物。此外，bHLH和bHLH拉链因子之间的转录协同作用还需要一种中间ETS蛋白，它可能连接bHLH因子的转录激活结构域。我们的观察结果定义了bHLH和ETS蛋白之间一种不同寻常的合作形式，并提出了组织限制性因子和普遍存在的因子结合以产生组织特异性增强子活性的机制。
