Specificity and robustness in transcription control networks

Specificity and robustness in transcription control networks
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DOI:
10.1073/pnas.022388499
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发表时间:
2002-02-19
影响因子:
11.1
通讯作者:
Shraiman, BI
Shraiman, BI
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Sengupta, AM;Djordjevic, M;Shraiman, BI

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转录因子对基因上游调控DNA元件的识别是调控基因表达的基本步骤。提供突变稳定性的必要性如何限制转录控制网络的组织?我们研究了一个转录因子与一组n个调控反应元件相互作用的突变负荷,作为因子/DNA结合特异性的函数,并从理论上得出结论,最佳特异性随着n的增加而降低。大肠杆菌基因组数据支持了(给定转录因子)结合位点变异性与其数量之间的预测相关性。利用转录因子/DNA结合生物物理模型提出的算法对大肠杆菌基因组数据进行分析。搜索候选转录因子结合位点的完整结果可在http://www.physics.rockefeller.edu/-boris/ public/search-ecoli上获得。
Recognition by transcription factors of the regulatory DNA elements upstream of genes is the fundamental step in controlling gene expression. How does the necessity to provide stability with respect to mutation constrain the organization of transcription control networks? We examine the mutation load of a transcription factor interacting with a set of n regulatory response elements as a function of the factor/DNA binding specificity and conclude on theoretical grounds that the optimal specificity decreases with n. The predicted correlation between variability of binding sites (for a given transcription factor) and their number is supported by the genomic data for Escherichia coli. The analysis of E. coli genomic data was carried out using an algorithm suggested by the biophysical model of transcription factor/DNA binding. Complete results of the search for candidate transcription factor binding sites are available at http://www.physics.rockefeller.edu/-boris/ public/search-ecoli.