Free Radical and Radiation Biology Program, Department of Radiation Oncology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242-1181, USA.
Antioxid Redox Signal. 2011 Jul 15;15(2):551-89. doi: 10.1089/ars.2010.3492. Epub 2011 Feb 5.
Epigenetic modifications represent mechanisms by which cells may effectively translate multiple signaling inputs into phenotypic outputs. Recent research is revealing that redox metabolism is an increasingly important determinant of epigenetic control that may have significant ramifications in both human health and disease. Numerous characterized epigenetic marks, including histone methylation, acetylation, and ADP-ribosylation, as well as DNA methylation, have direct linkages to central metabolism through critical redox intermediates such as NAD(+), S-adenosyl methionine, and 2-oxoglutarate. Fluctuations in these intermediates caused by both normal and pathologic stimuli may thus have direct effects on epigenetic signaling that lead to measurable changes in gene expression. In this comprehensive review, we present surveys of both metabolism-sensitive epigenetic enzymes and the metabolic processes that may play a role in their regulation. To close, we provide a series of clinically relevant illustrations of the communication between metabolism and epigenetics in the pathogenesis of cardiovascular disease, Alzheimer disease, cancer, and environmental toxicity. We anticipate that the regulatory mechanisms described herein will play an increasingly large role in our understanding of human health and disease as epigenetics research progresses.
表观遗传修饰代表了细胞将多种信号输入有效转化为表型输出的机制。最近的研究表明，氧化还原代谢是表观遗传控制的一个越来越重要的决定因素，它可能在人类健康和疾病中产生重大影响。许多已被描述的表观遗传标记，包括组蛋白甲基化、乙酰化和 ADP-核糖基化，以及 DNA 甲基化，通过关键的氧化还原中间体如 NAD(+)、S-腺苷甲硫氨酸和 2-氧戊二酸，与中心代谢直接联系。因此，正常和病理刺激引起的这些中间产物的波动可能对表观遗传信号直接产生影响，导致基因表达的可测量变化。在这篇全面的综述中，我们对代谢敏感的表观遗传酶以及可能在其调节中发挥作用的代谢过程进行了调查。最后，我们提供了一系列与心血管疾病、阿尔茨海默病、癌症和环境毒性发病机制中代谢与表观遗传之间通讯相关的临床相关实例。我们预计，随着表观遗传学研究的进展，本文所述的调节机制将在我们对人类健康和疾病的理解中发挥越来越大的作用。
