Department of Dermatology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, No. 139 Renmin Middle Rd, Changsha, 410011, Hunan, China.
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Suite 6510, 451 Health Sciences Drive, Davis, CA, 95616, USA.
Cell Mol Life Sci. 2018 Sep;75(18):3353-3369. doi: 10.1007/s00018-018-2864-2. Epub 2018 Jul 4.
Little information is available regarding mechanistic links between epigenetic modifications and autoimmune diseases. It seems plausible to surmise that aberrant gene expression and energy metabolism would disrupt immune tolerance, which could ultimately result in autoimmune responses. Metaboloepigenetics is an emerging paradigm that defines the interrelationships between metabolism and epigenetics. Epigenetic modifications, such as the methylation/demethylation of DNA and histone proteins and histone acetylation/deacetylation can be dynamically produced and eliminated by a group of enzymes that consume several metabolites derived from various physiological pathways. Recent insights into cellular metabolism have demonstrated that environmental stimuli such as dietary exposure and nutritional status act through the variation in concentration of metabolites to affect epigenetic regulation and breakdown biochemical homeostasis. Metabolites, including S-adenosylmethionine, acetyl-CoA, nicotinamide adenine dinucleotide, α-ketoglutarate, and ATP serve as cofactors for chromatin-modifying enzymes, such as methyltransferases, deacetylases and kinases, which are responsible for chromatin remodelling. The concentration of crucial nutrients, such as glucose, glutamine, and oxygen, spatially and temporally modulate epigenetic modifications to regulate gene expression and the reaction to stressful microenvironments in disease pathology. In this review, we focus on the interaction between metabolic intermediates and epigenetic modifications, integrating environmental signals with programmes through modification of the epigenome-metabolome to speculate as to how this may influence autoimmune diseases.
关于表观遗传修饰与自身免疫性疾病之间的机制联系，目前相关信息有限。可以合理推测，异常的基因表达和能量代谢会破坏免疫耐受，最终导致自身免疫反应。代谢表观遗传学是一个新兴的概念，定义了代谢与表观遗传学之间的相互关系。表观遗传修饰，如 DNA 和组蛋白的甲基化/去甲基化以及组蛋白乙酰化/去乙酰化，可以被一组消耗来自各种生理途径的多种代谢物的酶动态产生和消除。最近对细胞代谢的深入了解表明，环境刺激，如饮食暴露和营养状况，通过代谢物浓度的变化来影响表观遗传调控，破坏生化平衡。代谢物，包括 S-腺苷甲硫氨酸、乙酰辅酶 A、烟酰胺腺嘌呤二核苷酸、α-酮戊二酸和 ATP，作为染色质修饰酶（如甲基转移酶、去乙酰化酶和激酶）的辅助因子，负责染色质重塑。关键营养物质（如葡萄糖、谷氨酰胺和氧气）的浓度在时空上调节表观遗传修饰，以调节基因表达，并对疾病病理中的应激微环境做出反应。在这篇综述中，我们重点关注代谢中间产物与表观遗传修饰之间的相互作用，将环境信号与通过修饰表观基因组-代谢组的方案整合起来，推测这可能如何影响自身免疫性疾病。
