Davis T L, Firulli A B, Kinniburgh A J
Department of Human Genetics, Roswell Park Memorial Institute, Buffalo, NY 14263.
Proc Natl Acad Sci U S A. 1989 Dec;86(24):9682-6. doi: 10.1073/pnas.86.24.9682.
We have located a positive, cis-acting DNA sequence element within the 5' flanking DNA of the c-myc gene (-125 base pairs). This DNA sequence element has a large purine-pyrimidine strand asymmetry and can assume the H-DNA conformation. A factor with the properties of a ribonucleoprotein (RNP) interacts with this DNA region. The interaction of the c-myc DNA sequence element and the RNP involves an RNase H-sensitive mechanism and, therefore, may involve an RNA.DNA hybrid. In addition, a protein factor(s) binds to this DNA sequence element. DNA footprinting and mutant oligonucleotide binding/competition assays implicate a punctate, poly(G.C) recognition/binding sequence for the RNP factor, whereas the major protein factor requires two ACCCT sequence motifs for maximal binding. These results suggest that RNP and protein factors act as positive transcriptional regulators of the c-myc gene, perhaps by altering DNA topology.
我们在c-myc基因5'侧翼DNA(-125个碱基对)内定位到一个正向顺式作用DNA序列元件。该DNA序列元件具有较大的嘌呤-嘧啶链不对称性,并且能够呈现H-DNA构象。一种具有核糖核蛋白(RNP)特性的因子与该DNA区域相互作用。c-myc DNA序列元件与RNP的相互作用涉及一种对RNase H敏感的机制,因此可能涉及RNA-DNA杂交体。此外,一种蛋白质因子结合到该DNA序列元件上。DNA足迹法和突变寡核苷酸结合/竞争试验表明,RNP因子存在一个点状的、聚(G.C)识别/结合序列,而主要蛋白质因子需要两个ACCCT序列基序才能实现最大程度的结合。这些结果表明,RNP和蛋白质因子可能通过改变DNA拓扑结构,作为c-myc基因的正向转录调节因子发挥作用。