Research Institute, Nozaki Tokushukai Hospital, Daito City, Osaka, 574-0074, Japan.
Sci Rep. 2022 May 9;12(1):7549. doi: 10.1038/s41598-022-10998-z.
Expression of numerous genes is precisely controlled in a cell in various contexts. While genetic and epigenetic mechanisms contribute to this regulation, how each mechanism cooperates to ensure the proper expression patterns of the whole gene remains unclear. Here, I theoretically show that the repetition of simple biological processes makes cells functional with the appropriate expression patterns of all genes if the inappropriateness of current expression ratios is roughly fed back to the epigenetic states. A learning pair model is developed, in which two factors autonomously approach the target ratio by repeating two stochastic processes; competitive amplification with a small addition term and decay depending on the difference between the current and target ratios. Furthermore, thousands of factors are self-regulated in a hierarchical-pair architecture, in which the activation degrees competitively amplify, while transducing the activation signal, and decay at four different probabilities. Changes in whole-gene expression during human early embryogenesis and hematopoiesis are reproduced in simulation using this epigenetic learning process in a single genetically-determined hierarchical-pair architecture of gene regulatory cascades. On the background of this learning process, I propose the law of biological inertia, which means that a living cell basically maintains the expression pattern while renewing its contents.
在不同的环境中，细胞内的大量基因的表达都受到精确调控。尽管遗传和表观遗传机制对这种调控有贡献，但每种机制如何合作以确保整个基因的适当表达模式仍然不清楚。在这里，我从理论上表明，如果当前表达比率的不适当性被大致反馈到表观遗传状态，那么简单的生物过程的重复就可以使细胞具有适当的所有基因的表达模式。提出了一个学习对模型，其中两个因素通过重复两个随机过程自主接近目标比率；竞争放大，带有小的附加项，以及依赖于当前和目标比率之间的差异的衰减。此外，在层次对结构中，数千个因素可以自我调节，在这种结构中，激活程度通过竞争放大，同时传递激活信号，并以四个不同的概率衰减。在使用基因调控级联的单个遗传确定的层次对结构中的这种表观遗传学习过程进行模拟时，可以再现人类早期胚胎发生和造血过程中的整个基因表达变化。在这个学习过程的背景下，我提出了生物惯性定律，即活细胞在更新其内容的同时基本上保持表达模式。
