Schilling L J, Farnham P J
McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison 53706.
Crit Rev Eukaryot Gene Expr. 1994;4(1):19-53. doi: 10.1615/critreveukargeneexpr.v4.i1.20.
This review summarizes many studies that have used the mouse, hamster, or human dihydrofolate reductase locus as a model system for the study of basal or regulated transcription. This locus encodes two genes, dhfr and rep-3, that are oriented in opposite directions. The dhfr promoter and the two rep-3 promoters are highly GC-rich and do not contain consensus TATA boxes. The cis-acting elements important in basal transcription of these non-TATA box promoters have been mapped, revealing that Sp1 plays a dominant role, and that sequence elements both upstream and downstream of the initiation site contribute to transcriptional activity. Future studies will be directed toward understanding the assembly of transcription complexes on these promoters. The expression of the dhfr gene following treatment of cells with many different stimuli has been analyzed, and in many, but not all, cases the response has been at the transcriptional level. In those systems where the regulatory cis-acting element has been mapped, the E2F sites flanking the transcription initiation site play a central role in mediating the response. Future studies will be directed at characterizing the regulatory protein E2F and understanding how it interacts with the basal transcription complex at the dhfr promoter. The rep-3 gene contains two promoters that are both growth responsive: one promoter is regulated by E2F, the regulator of the other promoter has not been identified. In summary, the in-depth characterization of the 1 kb containing the dhfr and rep-3 promoters has begun to provide a detailed understanding of growth-responsive transcription.
本综述总结了许多将小鼠、仓鼠或人类二氢叶酸还原酶基因座用作基础转录或调控转录研究模型系统的研究。该基因座编码两个方向相反的基因，即dhfr和rep-3。dhfr启动子和两个rep-3启动子富含GC，且不包含共有TATA框。已对这些非TATA框启动子基础转录中重要的顺式作用元件进行了定位，结果表明Sp1起主导作用，且起始位点上下游的序列元件均对转录活性有贡献。未来的研究将致力于了解这些启动子上转录复合物的组装情况。已分析了用多种不同刺激处理细胞后dhfr基因的表达情况，在许多但并非所有情况下，反应都发生在转录水平。在那些已定位调控顺式作用元件的系统中，转录起始位点两侧的E2F位点在介导反应中起核心作用。未来的研究将致力于鉴定调控蛋白E2F，并了解其如何与dhfr启动子处的基础转录复合物相互作用。rep-3基因包含两个均对生长有反应的启动子：一个启动子受E2F调控，另一个启动子的调控因子尚未确定。总之，对包含dhfr和rep-3启动子的1 kb区域的深入表征已开始提供对生长反应性转录的详细理解。
