Departament de Fisica Fonamental, Facultat de Fisica, Universitat de Barcelona, Barcelona, Spain.
Biophys J. 2011 Oct 5;101(7):1569-79. doi: 10.1016/j.bpj.2011.08.041.
Much of the complexity observed in gene regulation originates from cooperative protein-DNA binding. Although studies of the target search of proteins for their specific binding sites on the DNA have revealed design principles for the quantitative characteristics of protein-DNA interactions, no such principles are known for the cooperative interactions between DNA-binding proteins. We consider a simple theoretical model for two interacting transcription factor (TF) species, searching for and binding to two adjacent target sites hidden in the genomic background. We study the kinetic competition of a dimer search pathway and a monomer search pathway, as well as the steady-state regulation function mediated by the two TFs over a broad range of TF-TF interaction strengths. Using a transcriptional AND-logic as exemplary functional context, we identify the functionally desirable regime for the interaction. We find that both weak and very strong TF-TF interactions are favorable, albeit with different characteristics. However, there is also an unfavorable regime of intermediate interactions where the genetic response is prohibitively slow.
基因调控中的许多复杂性源于蛋白质与 DNA 的协同结合。虽然对蛋白质在 DNA 上搜索其特定结合位点的目标搜索的研究已经揭示了蛋白质-DNA 相互作用的定量特征的设计原则，但对于 DNA 结合蛋白之间的协同相互作用，尚无此类原则。我们考虑了一个简单的理论模型，其中两个相互作用的转录因子（TF）物种搜索并结合隐藏在基因组背景中的两个相邻靶位点。我们研究了二聚体搜索途径和单体搜索途径的动力学竞争，以及两个 TF 在广泛的 TF-TF 相互作用强度下介导的稳态调节功能。我们使用转录 AND 逻辑作为示例功能上下文，确定了相互作用的功能可取范围。我们发现，弱和非常强的 TF-TF 相互作用都是有利的，尽管具有不同的特征。但是，也存在中间相互作用的不利范围，其中遗传反应非常缓慢。
