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基因表达的代谢编排:营养物质与表观基因组的相互作用。

Metabolic choreography of gene expression: nutrient transactions with the epigenome.

机构信息

Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.

出版信息

J Biosci. 2020;45.

Abstract

Eukaryotic complexity and thus their ability to respond to diverse cues are largely driven by varying expression of gene products, qualitatively and quantitatively. Protein adducts in the form of post-translational modifications, most of which are derived from metabolic intermediates, allow fine tuning of gene expression at multiple levels. With the advent of high-throughput and high-resolution mapping technologies there has been an explosion in terms of the kind of modifications on chromatin and other factors that govern gene expression. Moreover, even the classical notion of acetylation and methylation dependent regulation of transcription is now known to be intrinsically coupled to biochemical pathways, which were otherwise regarded as 'mundane'. Here we have not only reviewed some of the recent literature but also have highlighted the dependence of gene regulatory mechanisms on metabolic inputs, both direct and indirect. We have also tried to bring forth some of the open questions, and how our understanding of gene expression has changed dramatically over the last few years, which has largely become metabolism centric. Finally, metabolic regulation of epigenome and gene expression has gained much traction due to the increased incidence of lifestyle and age-related diseases.

摘要

真核生物的复杂性及其对各种信号的响应能力在很大程度上是由基因产物的定性和定量表达驱动的。蛋白质加合物以翻译后修饰的形式存在,其中大多数来源于代谢中间产物,允许在多个水平上精细调节基因表达。随着高通量和高分辨率作图技术的出现,关于染色质和其他控制基因表达的因素的修饰种类已经大量涌现。此外,即使是经典的依赖于乙酰化和甲基化的转录调控概念,现在也被认为与生化途径内在相关,而这些生化途径在以前被认为是“平凡的”。在这里,我们不仅回顾了一些最新的文献,还强调了基因调控机制对代谢输入的依赖,包括直接和间接的依赖。我们还试图提出一些悬而未决的问题,以及我们对基因表达的理解在过去几年中是如何发生巨大变化的,这些变化在很大程度上已经以代谢为中心。最后,由于生活方式和年龄相关疾病的发病率增加,代谢对表观基因组和基因表达的调节受到了更多的关注。

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