Institute of Functional Epigenetics, Helmholtz Zentrum München, Neuherberg, Germany.
Mol Metab. 2020 Aug;38:100955. doi: 10.1016/j.molmet.2020.01.019. Epub 2020 Feb 12.
Organisms can be primed by metabolic exposures to continue expressing response genes even once the metabolite is no longer available, and can affect the speed and magnitude of responsive gene expression during subsequent exposures. This "metabolic transcriptional memory" can have a profound impact on the survivability of organisms in fluctuating environments.
Here I present several examples of metabolic transcriptional memory in the microbial world and discuss what is known so far regarding the underlying mechanisms, which mainly focus on chromatin modifications, protein inheritance, and broad changes in metabolic network. From these lessons learned in microbes, some insights into the yet understudied human metabolic memory can be gained. I thus discuss the implications of metabolic memory in disease progression in humans - i.e., the memory of high blood sugar exposure and the resulting effects on diabetic complications.
Carbon source shifts from glucose to other less preferred sugars such as lactose, galactose, and maltose for energy metabolism as well as starvation of a signal transduction precursor sugar inositol are well-studied examples of metabolic transcriptional memory in Escherichia coli and Saccharomyces cerevisiae. Although the specific factors guiding metabolic transcriptional memory are not necessarily conserved from microbes to humans, the same basic mechanisms are in play, as is observed in hyperglycemic memory. Exploration of new metabolic transcriptional memory systems as well as further detailed mechanistic analyses of known memory contexts in microbes is therefore central to understanding metabolic memory in humans, and may be of relevance for the successful treatment of the ever-growing epidemic of diabetes.
生物体可以通过代谢暴露被激活，即使代谢物不再可用，它们也能继续表达响应基因，并影响随后暴露时响应基因表达的速度和幅度。这种“代谢转录记忆”对生物体在波动环境中的生存能力有深远的影响。
本文介绍了微生物世界中代谢转录记忆的几个例子，并讨论了目前已知的潜在机制，这些机制主要集中在染色质修饰、蛋白质遗传和代谢网络的广泛变化上。从这些在微生物中得到的经验教训中，可以对人类代谢记忆这一尚未深入研究的领域获得一些了解。因此，本文讨论了代谢记忆在人类疾病进展中的意义——即高血糖暴露的记忆及其对糖尿病并发症的影响。
在大肠杆菌和酿酒酵母中，碳源从葡萄糖向其他不太受欢迎的糖（如乳糖、半乳糖和麦芽糖）的能量代谢转变，以及信号转导前体糖肌醇的饥饿，都是代谢转录记忆的很好例子。尽管引导代谢转录记忆的具体因素在微生物到人类之间不一定保守，但相同的基本机制在起作用，正如高血糖记忆中观察到的那样。因此，探索新的代谢转录记忆系统，并对微生物中已知记忆环境进行更详细的机制分析，对于理解人类的代谢记忆至关重要，并且可能对成功治疗日益增长的糖尿病流行具有重要意义。
