Transcription factors are proteins that regulate gene activity by activating or repressing gene transcription. A special class of transcriptional repressors operates via a short-range mechanism, making local DNA regions inaccessible to binding by activators, and thus providing an indirect repressive action on the target gene. This mechanism is commonly modeled assuming that repressors interact with DNA under thermodynamic equilibrium and neglecting some configurations of the gene regulatory region. We elaborate on a more general nonequilibrium model of short-range repression using the graph formalism for transitions between gene states, and we apply analytical calculations to compare it with the equilibrium model in terms of the repression strength and expression noise. In contrast to the equilibrium approach, the new model allows us to separate two basic mechanisms of short-range repression. The first mechanism is associated with the recruiting of factors that mediate chromatin condensation, and the second one concerns the blocking of factors that mediate chromatin loosening. The nonequilibrium model demonstrates better performance on previously published gene expression data obtained for transcription factors controlling Drosophila development, and furthermore it predicts that the first repression mechanism is the most favorable in this system. The presented approach can be scaled to larger gene networks and can be used to infer specific modes and parameters of transcriptional regulation from gene expression data.

中文翻译：

---

基因转录调控中短程抑制的非平衡模型

转录因子是通过激活或抑制基因转录来调节基因活性的蛋白质。一类特殊的转录抑制因子通过短程机制起作用，使局部 DNA 区域无法被激活因子结合，从而对目标基因提供间接抑制作用。这种机制通常假设阻遏物在热力学平衡下与 DNA 相互作用并忽略基因调控区的某些配置。我们使用基因状态之间转换的图形形式详细说明了更一般的短程抑制的非平衡模型，并应用分析计算将其与平衡模型在抑制强度和表达噪声方面进行比较。与均衡方法相反，新模型使我们能够区分两种基本的短程压制机制。第一个机制与介导染色质凝聚的因子的募集有关，第二个机制与介导染色质松动的因子的阻断有关。非平衡模型在先前发表的用于转录因子控制的基因表达数据上表现出更好的性能果蝇发育，而且它预测第一个抑制机制在这个系统中是最有利的。所提出的方法可以扩展到更大的基因网络，并可用于从基因表达数据推断转录调控的特定模式和参数。