Nikolajczyk B S, Cortes M, Feinman R, Sen R
Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02254, USA.
Mol Cell Biol. 1997 Jul;17(7):3527-35. doi: 10.1128/MCB.17.7.3527.
A tripartite domain of the immunoglobulin mu heavy-chain gene enhancer that activates transcription in B cells contains binding sites for PU.1, Ets-1, and a leucine zipper-containing basic helix-loop-helix factor. Because PU.1 is expressed only in B cells and macrophages, we tested the activity of a minimal mu enhancer fragment in macrophages by transient transfections. The minimal mu enhancer activated transcription in macrophages, and the activity was dependent on all three sites. Analysis of mutated enhancers, in which spacing and orientation of the ETS protein binding sites had been changed, suggested that the mechanisms of enhancer activation were different in B cells and macrophages. Thus, ETS protein binding sites may be combined in different ways to generate tissue-specific transcription activators. Despite the activity of the minimal enhancer in macrophages, a larger mu enhancer fragment was inactive in these cells. We propose that formation of the nucleoprotein complex that is formed on the minimal enhancer in macrophages cannot be helped by the neighboring muE elements that are essential for activity of the monomeric enhancer.
免疫球蛋白μ重链基因增强子的一个三联体结构域可在B细胞中激活转录，该结构域包含PU.1、Ets-1以及一个含亮氨酸拉链的碱性螺旋-环-螺旋因子的结合位点。由于PU.1仅在B细胞和巨噬细胞中表达，我们通过瞬时转染检测了一个最小化μ增强子片段在巨噬细胞中的活性。最小化μ增强子在巨噬细胞中激活了转录，且该活性依赖于所有三个位点。对突变增强子的分析（其中ETS蛋白结合位点的间距和方向已改变）表明，增强子激活机制在B细胞和巨噬细胞中有所不同。因此，ETS蛋白结合位点可能以不同方式组合以产生组织特异性转录激活因子。尽管最小化增强子在巨噬细胞中有活性，但一个更大的μ增强子片段在这些细胞中无活性。我们提出，巨噬细胞中在最小化增强子上形成的核蛋白复合物无法得到对单体增强子活性至关重要的相邻μE元件的辅助。
