Sequence analysis of p53 response-elements suggests multiple binding modes of the p53 tetramer to DNA targets.
Sequence analysis of p53 response-elements suggests multiple binding modes of the p53 tetramer to DNA targets.
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p53响应元素的序列分析表明p53四聚体与DNA靶标的多种结合模式。
DOI：
10.1093/nar/gkm192
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发表时间：
2007
影响因子：
14.9
通讯作者：
Nussinov, Ruth
中科院分区：
文献类型：
--
作者：
Ma, Buyong;Pan, Yongping;Zheng, Jie;Levine, Arnold J;Nussinov, Ruth
p53 四聚体可特异性识别 20 bp DNA 元件。在这里，我们检查了 p53 响应元件 (p53RE) 中编码的对称性。我们分析了半位点以及全位点回文中的碱基倒置相关性。我们发现p53RE不仅是半位点的直接重复，而且是半位点的直接重复。相反，两个 p53 半位点耦合形成一个更高阶的 20bp 回文结构。人类基因组半位点之间的回文耦合比小鼠基因组更强。全位点回文和半位点回文由两个半位点之间的插入控制。最显着的特征是，四分之一位点 1 和 4 之间耦合（H14 耦合）的全位点回文在没有插入的 p53RE 中占主导地位。在人类 p53RE 中最常见的 3bp 插入增强了半位点回文结构。人类基因组中半位点之间耦合的统计频率与分组实验 p53 与 p53RE 的亲和力相关。对已知 p53RE 的检查表明，正向调节的 H14 偶联比负向调节的 p53RE 更强，阻遏物的 H14 偶联最低。我们认为回文序列耦合可能编码 p53 四聚体与 DNA 的潜在首选多重结合模式。
The p53 tetramer recognizes specifically a 20-bp DNA element. Here, we examined symmetries encoded in p53 response elements (p53REs). We analyzed base inversion correlations within the half-site, as well as in the full-site palindrome. We found that p53REs are not only direct repeats of half-sites; rather, two p53 half-sites couple to form a higher order 20 bp palindrome. The palindrome couplings between the half-sites are stronger for the human than for the mouse genome. The full-site palindrome and half-site palindrome are controlled by insertions between the two half-sites. The most notable feature is that the full-site palindrome with coupling between quarter-sites one and four (H14 coupling) dominates the p53REs without insertions. The most frequently observed insertion in human p53REs of 3 bp enhances the half-site palindrome. The statistical frequencies of the coupling between the half-sites in the human genome correlate with grouped experimental p53 affinities with p53REs. Examination of known p53REs indicates the H14 couplings are stronger for positive regulation than for negatively regulated p53REs, with repressors having the lowest H14 couplings. We propose that the palindromic sequence couplings may encode such potential preferred multiple binding modes of the p53 tetramer to DNA.