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Integration of transcriptional and metabolic control in macrophage activation
EMBO Reports ( IF 7.7 ) Pub Date : 2021-07-30 , DOI: 10.15252/embr.202153251
Gioacchino Natoli 1, 2 , Francesco Pileri 1 , Francesco Gualdrini 1 , Serena Ghisletti 1
Affiliation  

Macrophages react to microbial and endogenous danger signals by activating a broad panel of effector and homeostatic responses. Such responses entail rapid and stimulus-specific changes in gene expression programs accompanied by extensive rewiring of metabolism, with alterations in chromatin modifications providing one layer of integration of transcriptional and metabolic regulation. A systematic and mechanistic understanding of the mutual influences between signal-induced metabolic changes and gene expression is still lacking. Here, we discuss current evidence, controversies, knowledge gaps, and future areas of investigation on how metabolic and transcriptional changes are dynamically integrated during macrophage activation. The cross-talk between metabolism and inflammatory gene expression is in part accounted for by alterations in the production, usage, and availability of metabolic intermediates that impact the macrophage epigenome. In addition, stimulus-inducible gene expression changes alter the production of inflammatory mediators, such as nitric oxide, that in turn modulate the activity of metabolic enzymes thus determining complex regulatory loops. Critical issues remain to be understood, notably whether and how metabolic rewiring can bring about gene-specific (as opposed to global) expression changes.

中文翻译:

巨噬细胞活化中转录和代谢控制的整合

巨噬细胞通过激活广泛的效应和稳态反应对微生物和内源性危险信号作出反应。这种反应需要基因表达程序的快速和刺激特异性变化,伴随着代谢的广泛重新布线,染色质修饰的改变提供了转录和代谢调节的一层整合。仍然缺乏对信号诱导的代谢变化和基因表达之间的相互影响的系统和机械理解。在这里,我们讨论了巨噬细胞激活过程中代谢和转录变化如何动态整合的当前证据、争议、知识差距和未来研究领域。代谢和炎症基因表达之间的串扰部分归因于影响巨噬细胞表观基因组的代谢中间体的产生、使用和可用性的改变。此外,刺激诱导的基因表达变化会改变炎症介质(如一氧化氮)的产生,进而调节代谢酶的活性,从而决定复杂的调节环。关键问题仍有待理解,特别是代谢重新布线是否以及如何导致基因特异性(而不是全局)表达变化。反过来调节代谢酶的活性,从而决定复杂的调节环。关键问题仍有待理解,特别是代谢重新布线是否以及如何导致基因特异性(而不是全局)表达变化。反过来调节代谢酶的活性,从而决定复杂的调节环。关键问题仍有待理解,特别是代谢重新布线是否以及如何导致基因特异性(而不是全局)表达变化。
更新日期:2021-09-06
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