PDF(Pubmed)
Abstract：
Interacting molecules create regulatory architectures that can persist despite turnover of molecules. Although epigenetic changes occur within the context of such architectures, there is limited understanding of how they can influence the heritability of changes. Here, I develop criteria for the heritability of regulatory architectures and use quantitative simulations of interacting regulators parsed as entities, their sensors, and the sensed properties to analyze how architectures influence heritable epigenetic changes. Information contained in regulatory architectures grows rapidly with the number of interacting molecules and its transmission requires positive feedback loops. While these architectures can recover after many epigenetic perturbations, some resulting changes can become permanently heritable. Architectures that are otherwise unstable can become heritable through periodic interactions with external regulators, which suggests that mortal somatic lineages with cells that reproducibly interact with the immortal germ lineage could make a wider variety of architectures heritable. Differential inhibition of the positive feedback loops that transmit regulatory architectures across generations can explain the gene-specific differences in heritable RNA silencing observed in the nematode Caenorhabditis elegans. More broadly, these results provide a foundation for analyzing the inheritance of epigenetic changes within the context of the regulatory architectures implemented using diverse molecules in different living systems.
摘要：
相互作用的分子产生可持续的调控结构,尽管分子周转。尽管表观遗传变化发生在这种结构的背景下，对它们如何影响变化的遗传性的理解有限。这里,我制定了监管架构的遗传力标准，并使用解析为实体的相互作用的监管机构的定量模拟，他们的传感器，和感知属性来分析体系结构如何影响可遗传的表观遗传变化。监管架构中包含的信息随着相互作用分子的数量而迅速增长，其传输需要正反馈回路。虽然这些架构可以在许多表观遗传扰动后恢复，一些由此产生的变化可以永久遗传。通过与外部监管机构的定期互动，否则不稳定的架构可能会变得可遗传，这表明，具有可重复地与不朽细菌谱系相互作用的细胞的凡人体细胞谱系可以使更多种类的体系结构可遗传。在线虫秀丽隐杆线虫中观察到的可遗传RNA沉默中正反馈回路的差异抑制可以解释。更广泛地说,这些结果为在不同生命系统中使用不同分子实施的调控结构的背景下分析表观遗传变化的遗传提供了基础。
