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Bio-Logic: Gene Expression and the Laws of Combinatorial Logic

机译：生物逻辑：基因表达和组合逻辑定律

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At the heart of the development of fertilized eggs into fully formed organisms and the adaptation of cells to changed conditions are genetic regulatory networks (GRNs). In higher multicellular organisms, signal selection and multiplexing are performed at the cis-regulatory domains of genes, where combinations of transcription factors (TFs) regulate the rates at which the genes are transcribed into mRNA. To be able to act as activators or repressors of gene transcription, TFs must first bind to target sequences on the regulatory domains. Two TFs that act in concert may bind entirely independently of each other, but more often binding of the first one will alter the affinity of the other for its binding site. This article presents a systematic investigation into the effect of TF binding dependences on the predicted regulatory function of this bio-logic. Four extreme scenarios, commonly used to classify enzyme activation and inhibition patterns, for the binding of two TFs were explored: independent (the TFs bind without affecting each other's affinities), competitive (the TFs compete for the same binding site), ordered (the TFs bind in a compulsory order), and joint binding (the TFs either bind as a preformed complex, or binding of one is virtually impossible in the absence of the other). The conclusions are: (1) the laws of combinatorial logic hold only for systems with independently binding TFs; (2) systems formed according to the other scenarios can mimic the functions of their Boolean logical counterparts, but cannot be combined or decomposed in the same way; and (3) the continuously scaled output of systems consisting of competitively binding activators and repressors can be controlled more robustly than that of single TF or (quasi-)logical multi-TF systems.
机译：基因调控网络（GRN）是受精卵发展为完全形成的有机体并使细胞适应变化的条件的核心。在更高的多细胞生物中，信号的选择和多重化是在基因的顺式调节域进行的，其中转录因子（TF）的组合调节基因转录成mRNA的速率。为了能够充当基因转录的激活物或阻遏物，TF必须首先结合调节域上的靶序列。协同作用的两个TF可能彼此完全独立地结合，但是更经常地，第一个TF的结合会改变另一个TF的结合位点。本文提出了对TF结合依赖性对这种生物制剂的预测调控功能的影响的系统研究。针对两种TF的结合，探讨了通常用于对酶激活和抑制模式进行分类的四种极端情况：独立（TF结合而互不影响彼此的亲和力），竞争性（TF竞争相同的结合位点），有序的（ TF以强制顺序进行绑定）和联合绑定（TF作为预先形成的复合体进行绑定，或者在没有其他TF的情况下实际上不可能进行绑定）。结论是：（1）组合逻辑定律仅适用于具有独立绑定TF的系统； （2）根据其他场景构成的系统可以模仿其布尔逻辑对应物的功能，但不能以相同的方式组合或分解； （3）由竞争性结合的激活剂和阻遏物组成的系统的连续缩放输出可以比单个TF或（准）逻辑多TF系统更可靠地控制。

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