Hen R, Borrelli E, Fromental C, Sassone-Corsi P, Chambon P
Nature. 1986;321(6067):249-51. doi: 10.1038/321249a0.
Enhancers stimulate transcription of several eukaryotic genes (for review see ref. 1). While some enhancers, like that of simian virus 40 (SV40), are active in a wide range of cell types, others are more cell-specific. For example, the polyoma virus (Py) enhancer is not active in undifferentiated embryonal carcinoma (EC) cells, such as F9 cells, while it is active in differentiated cells. In contrast, the SV40 enhancer is active in both undifferentiated and differentiated EC cells. One possible explanation for this difference is that the two viral enhancers interact with different positively or negatively acting transcription factors, a notion supported by in vitro experiments showing that the Py enhancer interacts with proteins that do not bind to the SV40 enhancer. Some viral and cellular enhancers, including the Py and SV40 enhancers, can be negatively regulated by the products of the E1A transcription unit of adenovirus-2. As it has been postulated that undifferentiated F9 cells contain an E1A-like activity, it is possible that the latter is responsible for the lack of activity of the Py enhancer in these cells. We show here that the E1A products do not repress a point mutant of the Py enhancer (Py ECF9.1; ref. 11 and references therein) that is active in undifferentiated F9 cells. This result is consistent with the idea that undifferentiated F9 cells contain a cellular repressor that blocks the Py enhancer and that this repressor has the same target sequence as the E1A proteins.
增强子可刺激多种真核基因的转录(综述见参考文献1)。虽然有些增强子,如猴病毒40(SV40)的增强子,在多种细胞类型中都有活性,但其他增强子则具有更强的细胞特异性。例如,多瘤病毒(Py)增强子在未分化的胚胎癌细胞(如F9细胞)中无活性,而在分化细胞中具有活性。相比之下,SV40增强子在未分化和分化的胚胎癌细胞中均有活性。对此差异的一种可能解释是,这两种病毒增强子与不同的正性或负性作用转录因子相互作用,体外实验支持了这一观点,该实验表明Py增强子与不结合SV40增强子的蛋白质相互作用。一些病毒和细胞增强子,包括Py和SV40增强子,可被腺病毒2的E1A转录单位的产物负调控。由于推测未分化的F9细胞含有类似E1A的活性,因此后者可能是Py增强子在这些细胞中缺乏活性的原因。我们在此表明,E1A产物不会抑制在未分化F9细胞中有活性的Py增强子的点突变体(Py ECF9.1;参考文献11及其中的参考文献)。这一结果与以下观点一致,即未分化的F9细胞含有一种细胞阻遏物,该阻遏物可阻断Py增强子,且这种阻遏物与E1A蛋白具有相同的靶序列。