Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions, such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks remains a major challenge. Here, we use a well-defined synthetic gene regulatory network to study how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one gene regulatory network with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Our results demonstrate that changes in local genetic context can place a single transcriptional unit within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual transcriptional units, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of gene regulatory networks.

中文翻译：

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当地的遗传环境影响着基因调控网络的功能

基因表达水平受多种共存分子机制的影响。这些相互作用中的一些，例如转录因子和启动子的相互作用已经被广泛研究。然而，预测基因调控网络的表型仍然是一项重大挑战。在这里，我们使用定义明确的合成基因调控网络来研究网络表型如何依赖于本地遗传背景，即转录因子的遗传邻域及其相对位置。我们显示具有固定拓扑结构的一个基因调控网络不仅可以定量显示，而且可以定性显示不同的表型，这完全取决于其组成部分的局部遗传背景。我们的结果表明，本地遗传背景的变化可以将单个转录单位置于两个独立的调控区中，而无需复杂的调控序列。我们提出，各个转录单位的相对顺序及其可能的组合复杂性，在塑造基因调控网络表型中起着重要作用。