Synergistic transcriptional enhancement does not depend on the number of acidic activation domains bound to the promoter.
Synergistic transcriptional enhancement does not depend on the number of acidic activation domains bound to the promoter.
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协同转录增强不依赖于与启动子结合的酸性激活结构域的数量。
DOI：
10.1073/pnas.88.1.224
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发表时间：
1991
影响因子：
11.1
通讯作者：
Struhl,K
中科院分区：
文献类型：
--
作者：
Oliviero,S;Struhl,K
许多真核转录激活蛋白含有与特异性启动子序列相互作用的DNA结合结构域和刺激转录所需的酸性激活区。这种激活蛋白的转录增强通常是协同和混杂的;含有单个蛋白或甚至不相关蛋白的多个结合位点的启动子的活性可以比具有单个位点的启动子高10-100倍。已经表明，这种协同作用反映了基本转录机制对酸性激活区域的数量和/或质量的非线性响应。在这里，我们确定的Jun-Fos异源二聚体的转录活性含有一个或两个GCN 4酸性激活区的启动子上含有一个或两个Ap-1的靶位点。令人惊讶的是，具有一个或两个酸性区域的异二聚体以相似的效率激活转录，并且在含有两个靶位点的启动子上具有同等的协同作用（10至15倍）。因此，转录协同作用不依赖于酸性激活区的数量，而是依赖于与启动子结合的蛋白质的数量。这表明协同作用是通过协同DNA结合或通过替代机制介导的，其中DNA结合结构域在转录中起更直接的作用（例如，DNA结构的变化、核小体置换或与转录机制的直接相互作用）。
Many eukaryotic transcriptional activator proteins contain a DNA-binding domain that interacts with specific promoter sequences and an acidic activation region that is required to stimulate transcription. Transcriptional enhancement by such activator proteins is often synergistic and promiscuous; promoters containing multiple binding sites for an individual protein or even for unrelated proteins can be 10-100 times more active than promoters with single sites. It has been suggested that such synergy reflects a nonlinear response of the basic transcription machinery to the number and/or quality of acidic activation regions. Here, we determine the transcriptional activity of Jun-Fos heterodimers containing one or two GCN4 acidic activation regions on promoters containing one or two Ap-1 target sites. Surprisingly, heterodimers with one or two acidic regions activate transcription with similar efficiency and are equally synergistic (10- to 15-fold) on promoters containing two target sites. Thus, transcriptional synergy does not depend on the number of acidic activation regions but rather on the number of proteins bound to the promoter. This suggests that synergy is mediated either by cooperative DNA binding or by alternative mechanisms in which the DNA-binding domain plays a more direct role in transcription (e.g., changes in DNA structure, nucleosome displacement, or direct interactions with the transcriptional machinery).