MacLeod M C
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville 78957.
Nucleic Acids Res. 1993 Mar 25;21(6):1439-47. doi: 10.1093/nar/21.6.1439.
We have analyzed predicted helical twist angles in the 21-bp repeat region of the SV40 genome, using a semi-empirical model previously shown to accurately predict backbone conformations. Unexpectedly, the pattern of twist angles characteristic of the six GC-boxes is repeated an additional five times at positions that are regularly interspersed with the six GC-box sequences. These patterns of helical twist angles are associated with a second, imperfectly-repeated sequence motif, the TR-box 5'-RRNTRGG. Unrelated DNA sequences that interact with trans-acting factors (p53 and GABP) exhibit similar twist angle patterns, due to elements of the general form 5'-RRRYRRR that occur as interspersed arrays with a spacing of 10-11 bp and an offset of 4-6 bp. Arrays of these elements, which we call pyrimidine sandwich elements (PSEs), may play an important role in the interaction of trans-acting factors with DNA control regions. In 13 human proto-oncogenes analyzed, we identified 31 PSE arrays, 11 of which were in the 5'-flanking regions of the genes. The most extensive array was found in the promoter region of the K-ras gene. Extending over 80 bp of DNA, it contained 16 PSEs that showed an average deviation from the SV40 criterion pattern of angles of only 1.2 degrees.
我们使用先前已证明能准确预测主链构象的半经验模型，分析了SV40基因组21碱基对重复区域中预测的螺旋扭转角。出乎意料的是，六个GC盒特有的扭转角模式在与六个GC盒序列规则间隔分布的位置上又重复出现了五次。这些螺旋扭转角模式与第二个不完全重复的序列基序相关，即TR盒5'-RRNTRGG。与反式作用因子（p53和GABP）相互作用的无关DNA序列，由于一般形式为5'-RRRYRRR的元件以间隔10 - 11碱基对且偏移4 - 6碱基对的形式作为散布阵列出现，所以呈现出相似的扭转角模式。这些元件阵列，我们称之为嘧啶夹心元件（PSEs），可能在反式作用因子与DNA调控区域的相互作用中发挥重要作用。在分析的13个人类原癌基因中，我们鉴定出31个PSE阵列，其中11个位于基因的5'侧翼区域。在K-ras基因的启动子区域发现了最广泛的阵列。它延伸超过80碱基对的DNA，包含16个PSE，其角度与SV40标准模式的平均偏差仅为1.2度。
