Nussinov R
Laboratory of Mathematical Biology, NCI-Frederick Cancer Research and Developmental Center, Maryland 21702-1201.
J Biomol Struct Dyn. 1992 Jun;9(6):1213-37. doi: 10.1080/07391102.1992.10507988.
Regulation of gene expression in eukaryotes involves a complex assembly of DNA recognition sequence elements and their respective protein factors. The upstream promoter/enhancer sequences are position and orientation independent. Despite their variable distances from the TATA box and transcription start site, interaction between the protein activators and TATA general transcription factors takes place, enabling induced levels of transcription initiation. Here the intervening sequences between the GC and TATA boxes are examined as functions of their lengths. Regardless of the substantial differences in the spacer sizes, similar mono and dinucleotide distributions are noted. Purine-purine base pair steps, except for AA, are more frequent at and near the GC box in the 5' ends of the loops than in their 3' ends. Pyrimidine-pyrimidine base pair steps, except for TT behave similarly. AT and TA (as well as AA and TT) are more frequent in the 3' ends of the loops near the TATA. Examination of these distributions, as well as of the sequences composing the GC and TATA boxes indicates that the DNA in the upstream part of the loop is more rigid, whereas the downstream regions are far more flexible. The flexibility of the general TATA region may afford correct spatial juxtapositioning of the proteins with respect to each other, enabling interactions between the activators and the general transcription factors.
真核生物中基因表达的调控涉及DNA识别序列元件及其各自蛋白质因子的复杂组装。上游启动子/增强子序列与位置和方向无关。尽管它们与TATA盒和转录起始位点的距离可变，但蛋白质激活剂与TATA通用转录因子之间仍会发生相互作用，从而实现诱导水平的转录起始。在此，研究了GC盒和TATA盒之间的间隔序列与其长度的关系。无论间隔大小存在多大差异，单核苷酸和二核苷酸分布都相似。除了AA之外，嘌呤-嘌呤碱基对步骤在环的5'端的GC盒处及其附近比在其3'端更频繁。嘧啶-嘧啶碱基对步骤，除了TT之外，表现类似。AT和TA（以及AA和TT）在TATA附近的环的3'端更频繁。对这些分布以及构成GC盒和TATA盒的序列的研究表明，环上游部分的DNA更刚性，而下游区域则更灵活。通用TATA区域的灵活性可能使蛋白质彼此正确地空间并置，从而实现激活剂与通用转录因子之间的相互作用。
