Kumano M, Nakagawa T, Imamura Y, Galli I, Ariga H, Iguchi-Ariga S M
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
FEBS Lett. 1992 Sep 7;309(2):146-52. doi: 10.1016/0014-5793(92)81083-x.
In earlier studies we had shown that a transcriptional enhancer sequence exists about 2 kb upstream of the human c-myc gene. The core sequence necessary for enhancer activity was defined therein as a 21 bp nucleotide element, which also showed autonomous replicating activity [EMBO J. (1988) 7, 3135-3142; EMBO J. (1989) 8, 4273-4279]. Recently, several reports have substantiated the notion that transcription and replication can be concertedly regulated in a larger number of cases than expected. In this report, we took the simian virus 40 (SV 40) ori/promoter as a model system. The SV40 enhancer is known to enhance transcription from its ori/promoter, but to reduce its replication (probably due to a negative feedback). The SV40 enhancer was replaced by the c-myc enhancer core in order to see its effect upon SV40 DNA replication and transcription. The results showed that besides stimulating transcription, the c-myc enhancer promoted SV40 DNA replication in monkey CosI cells. Stimulation was only observed when the c-myc enhancer was inserted in the 'up-to-down' orientation to the SV40 promoter. The promoting function of the c-myc enhancer on DNA replication correlated with the transcriptional activation function, as determined by systematic point mutations introduced within the 21 bp core sequence.
在早期研究中，我们已表明在人类c-myc基因上游约2 kb处存在一个转录增强子序列。其中定义的增强子活性所需的核心序列为一个21 bp的核苷酸元件，其也表现出自主复制活性[《欧洲分子生物学组织杂志》（1988年）7卷，3135 - 3142页；《欧洲分子生物学组织杂志》（1989年）8卷，4273 - 4279页]。最近，几份报告证实了这样一种观点，即在比预期更多的情况下，转录和复制可以协同调节。在本报告中，我们以猴病毒40（SV 40）ori/启动子作为模型系统。已知SV40增强子可增强其ori/启动子的转录，但会降低其复制（可能是由于负反馈）。将SV40增强子替换为c-myc增强子核心，以观察其对SV40 DNA复制和转录的影响。结果表明，除了刺激转录外，c-myc增强子还促进了猴CosI细胞中SV40 DNA的复制。仅当c-myc增强子以“自上而下”的方向插入到SV40启动子时才观察到刺激作用。通过在21 bp核心序列内引入的系统点突变确定，c-myc增强子对DNA复制的促进功能与转录激活功能相关。
