arXiv physics/01120832001-12physics.bio-phcond-mat.stat-mechq-bio.BM

转录因子与DNA相互作用的物理限制和功能特征

Physical Constraints and Functional Characteristics of Transcription Factor-DNA Interaction

Ulrich Gerland, J. David Moroz, Terence Hwa

备注：: 9 pages, 4 figures; revised version as published in PNAS
发表信息：: Proc. Natl. Acad. Sci. USA 99 (2002) 12015-20
DOI：: 10.1073/pnas.192693599

摘要：

我们研究了细菌中转录因子-DNA相互作用的理论“设计原理”，特别关注转录因子（TF）与基因组背景（即，没有靶位点的基因组）。我们引入并激发了“可编程性”的概念，即仅仅通过突变靶位点的结合序列来在宽范围内设置TF结合的阈值浓度的能力。这一功能需求，连同TF-DNA相互作用的热力学和动力学所产生的物理约束，使我们的“最佳”相互作用参数的范围很窄。我们发现，这个参数集与一些示例性原核TF的相互作用参数的实验数据吻合得很好。这表明TF-DNA相互作用确实是可编程的。我们建议进一步的实验来测试这是否是一个大类TF的一般功能。

英文摘要：

We study theoretical ``design principles'' for transcription factor-DNA interaction in bacteria, focusing particularly on the statistical interaction of the transcription factors (TF's) with the genomic background (i.e., the genome without the target sites). We introduce and motivate the concept of `programmability', i.e. the ability to set the threshold concentration for TF binding over a wide range merely by mutating the binding sequence of a target site. This functional demand, together with physical constraints arising from the thermodynamics and kinetics of TF-DNA interaction, leads us to a narrow range of ``optimal'' interaction parameters. We find that this parameter set agrees well with experimental data for the interaction parameters of a few exemplary prokaryotic TF's. This indicates that TF-DNA interaction is indeed programmable. We suggest further experiments to test whether this is a general feature for a large class of TF's.

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