Biological Activity and Modular Structure of RE-1-silencing Transcription Factor (REST), a Repressor of Neuronal Genes*
Biological Activity and Modular Structure of RE-1-silencing Transcription Factor (REST), a Repressor of Neuronal Genes*
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DOI：
10.1074/jbc.273.41.26891
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发表时间：
1998-10
期刊：
影响因子：
--
通讯作者：
G. Thiel;M. Lietz;M. Cramer
中科院分区：
文献类型：
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作者：
G. Thiel;M. Lietz;M. Cramer
锌指蛋白RE-1沉默转录因子（REST）1是一种转录抑制因子，抑制非神经元组织中的神经元基因。使用REST表达载体的神经母细胞瘤细胞的转染实验显示，突触蛋白I启动子活性由REST控制。使用一组含有强启动子/增强子和REST结合位点的模型启动子进一步研究REST的生物活性。当来自编码突触蛋白I、SCG 10、α1-甘氨酸受体、神经元烟碱乙酰胆碱受体的β2-亚基和毒蕈碱乙酰胆碱受体的m4-亚基的基因的REST结合基序存在于启动子区域中时，REST起转录抑制剂的作用。检测到这些REST结合基序的生物活性没有差异。此外，我们发现REST在远处作为转录抑制因子非常有效。因此，REST代表了一种通用的转录阻遏物，其阻断转录，而不管其结合位点相对于增强子和启动子的位置或方向如何。这种生物活性也可以归因于REST的孤立结构域。在REST的N和C末端鉴定的两个阻遏物结构域可转移到异源DNA结合结构域，并且从近端和远端位置起作用，类似于REST蛋白。
The zinc finger protein RE-1-silencing transcription factor (REST)1 is a transcriptional repressor that represses neuronal genes in nonneuronal tissues. Transfection experiments of neuroblastoma cells using a REST expression vector revealed that synapsin I promoter activity is controlled by REST. The biological activity of REST was further investigated using a battery of model promoters containing strong promoters/enhancers and REST binding sites. REST functioned as a transcriptional repressor when REST binding motifs derived from the genes encoding synapsin I, SCG10, α1-glycine receptor, the β2-subunit of the neuronal nicotinic acetylcholine receptor, and the m4-subunit of the muscarinic acetylcholine receptor were present in the promoter region. No differences in the biological activity of these REST binding motifs tested were detected. Moreover, we found that REST functioned very effectively as a transcriptional repressor at a distance. Thus, REST represents a general transcriptional repressor that blocks transcription regardless of the location or orientation of its binding site relative to the enhancer and promoter. This biological activity could also be attributed to isolated domains of REST. Both repressor domains identified at the N and C termini of REST were transferable to a heterologous DNA binding domain and functioned from proximal and distal positions, similar to the REST protein.