Benham C J
Department of Biomathematical Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Mol Biol. 1996 Jan 26;255(3):425-34. doi: 10.1006/jmbi.1996.0035.
Analytic methods that accurately calculate the extent of duplex destabilization induced in each base-pair of a DNA molecule by superhelical stresses are used to analyze several genomic DNA sequences. Sites predicted to be susceptible to stress-induced duplex destabilization (SIDD) are found to be closely associated with specific transcriptional regulatory regions. Operators within the promoters of SOS-regulated Escherichia coli genes are destabilized by superhelical stresses, whereas closely related sequences present elsewhere on that genome are not. Analysis of genomic sequences from the budding yeast Saccharomyces cerevisiae finds a distinctive tripartite pattern, in which the 3' and 5' termini of genes are destabilized, but the sequence encoding the primary transcript is not. Three rDNA genes from higher eukaryotes exhibit a similar pattern. Implications of these results regarding possible mechanisms of activity of the regions involved are discussed. A strategy is presented for designing experiments in which the susceptibility to SIDD of a local region is altered without changing its local base sequence. The occurrence of the observed SIDD patterns provides a new approach to searching uncharacterized genomic sequences for transcriptionally active regions.
利用能精确计算超螺旋应力在DNA分子每个碱基对中所诱导的双链解链程度的分析方法，对多个基因组DNA序列进行分析。发现预测易受应力诱导双链解链（SIDD）影响的位点与特定转录调控区域密切相关。SOS调控的大肠杆菌基因启动子内的操纵子会因超螺旋应力而解链，而该基因组其他位置存在的密切相关序列则不会。对芽殖酵母酿酒酵母基因组序列的分析发现了一种独特的三方模式，即基因的3'和5'末端解链，但编码初级转录本的序列不解链。来自高等真核生物的三个核糖体DNA基因呈现出类似模式。讨论了这些结果对相关区域可能的活性机制的影响。提出了一种设计实验的策略，在该实验中，局部区域对SIDD的敏感性在不改变其局部碱基序列的情况下发生改变。所观察到的SIDD模式的出现为在未表征的基因组序列中搜索转录活性区域提供了一种新方法。
