Dawson S J, Yoon S O, Chikaraishi D M, Lillycrop K A, Latchman D S
Department of Molecular Pathology, University College London Medical School, UK.
Nucleic Acids Res. 1994 Mar 25;22(6):1023-8. doi: 10.1093/nar/22.6.1023.
The tyrosine hydroxylase (TH) gene promoter contains adjacent octamer and heptamer motifs which act as target sites for octamer binding transcription factors. Mutation of the heptamer motif but not the octamer motif enhances TH promoter activity in neuronal cells expressing Oct-2 but not in non-expressing fibroblasts. Similarly addition of the heptamer motif to a minimal TH promoter represses gene expression in neuronal cells but not in fibroblasts. These effects can be reproduced by the artificial expression of neuronal isoforms of Oct-2 in fibroblasts which results in the repression of transfected TH promoters containing an intact heptamer motif but not those in which this motif has been mutated or deleted. The TH promoter thus represents the first example of a cellular promoter which is repressed by Oct-2. The significance of this effect is discussed in terms of the cell type specificity of the TH promoter and its induction by different physiological stimuli.
酪氨酸羟化酶（TH）基因启动子包含相邻的八聚体和七聚体基序，它们作为八聚体结合转录因子的靶位点。七聚体基序而非八聚体基序的突变增强了在表达Oct-2的神经元细胞中TH启动子的活性，但在不表达Oct-2的成纤维细胞中则不然。同样，将七聚体基序添加到最小的TH启动子中会抑制神经元细胞中的基因表达，但不会抑制成纤维细胞中的基因表达。这些效应可以通过在成纤维细胞中人工表达Oct-2的神经元异构体来重现，这会导致含有完整七聚体基序的转染TH启动子受到抑制，但不影响该基序已发生突变或缺失的启动子。因此，TH启动子代表了第一个被Oct-2抑制的细胞启动子的例子。本文从TH启动子的细胞类型特异性及其受不同生理刺激诱导的角度讨论了这种效应的意义。
