物理限制决定了细菌启动子结构的逻辑
Physical constraints determine the logic of bacterial promoter architectures
摘要：
位点特异性转录因子（TF）与DNA上的靶位点结合，在那里它们调节基因转录的速率。细菌TF在寻找它们的靶位点时经历易化扩散（DNA上的3D扩散和1D随机游走的组合）。使用计算机模拟的搜索过程中，我们表明，组织的结合位点，连同TF拷贝数和结合位点的亲和力，起着重要的作用，不仅在确定启动子占用的稳定状态，但也在TF结合的顺序。这些效应可以通过基于促进扩散的模型来捕获，但不能通过标准热力学来捕获。我们发现，结合位点的间距编码复杂的逻辑，这可以从三个基本的积木的组合：开关，障碍和集群，其响应单独和更高的组织，我们详细地解释。有效的启动子组织通常存在于E.大肠杆菌基因组，菌株之间高度保守。这将使基因调控的研究在一个前所未有的细节水平，在我们的框架可以创建启动子逻辑的可检验的假设。
英文摘要：
Site-specific transcription factors (TFs) bind to their target sites on the DNA, where they regulate the rate at which genes are transcribed. Bacterial TFs undergo facilitated diffusion (a combination of 3D diffusion around and 1D random walk on the DNA) when searching for their target sites. Using computer simulations of this search process, we show that the organisation of the binding sites, in conjunction with TF copy number and binding site affinity, plays an important role in determining not only the steady state of promoter occupancy, but also the order at which TFs bind. These effects can be captured by facilitated diffusion-based models, but not by standard thermodynamics. We show that the spacing of binding sites encodes complex logic, which can be derived from combinations of three basic building blocks: switches, barriers and clusters, whose response alone and in higher orders of organisation we characterise in detail. Effective promoter organizations are commonly found in the E. coli genome and are highly conserved between strains. This will allow studies of gene regulation at a previously unprecedented level of detail, where our framework can create testable hypothesis of promoter logic.
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