Evans T, DeChiara T, Efstratiadis A
Department of Genetics and Development, Columbia University, New York, NY 10032.
J Mol Biol. 1988 Jan 5;199(1):61-81. doi: 10.1016/0022-2836(88)90379-8.
We have characterized the cis-control signals in one of the two promoters of the developmentally regulated rat insulin-like growth factor II gene (rIGF-II) by a combination of in-vivo transient expression, in-vitro transcription, footprinting, gel band-shifting and methylation-interference experiments, using a series of deletion mutant templates. Our results indicate that this simple (minimal) promoter (P2) consists of no more than 128 base-pairs, which include an ATA box and four proximal upstream GC boxes binding the general transcription factor Sp1. Three of the latter sites deviate from the known Sp1 consensus recognition sequence. The two types of cis-acting regulatory signals (GC/ATA motif) of the P2 promoter are inter-dependent and sufficient for transcription. A model for the operation of this type of minimal promoter is discussed. S1 nuclease-hypersensitive sites, localized by in-vitro mapping to the region of the P2 Sp1-binding sites, are also present in vivo and correlate with the transcriptional state of chromatin in the rIGF-II locus. We show that recognition sites for Sp1 binding are a subset of sequences that exhibit hypersensitivity to S1.
我们通过体内瞬时表达、体外转录、足迹法、凝胶带迁移和甲基化干扰实验相结合的方法,使用一系列缺失突变模板,对发育调控的大鼠胰岛素样生长因子II基因(rIGF-II)两个启动子之一中的顺式调控信号进行了表征。我们的结果表明,这个简单(最小)启动子(P2)由不超过128个碱基对组成,其中包括一个ATA框和四个结合通用转录因子Sp1的近端上游GC框。后三个位点偏离了已知的Sp1共有识别序列。P2启动子的两种顺式作用调控信号(GC/ATA基序)相互依赖且足以进行转录。讨论了这种类型最小启动子的运作模型。通过体外定位到P2 Sp1结合位点区域的S1核酸酶超敏位点在体内也存在,并且与rIGF-II基因座中染色质的转录状态相关。我们表明,Sp1结合的识别位点是对S1表现出超敏性的序列子集。