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The redox basis of epigenetic modifications: from mechanisms to functional consequences
Journal article   Open access   Peer reviewed

The redox basis of epigenetic modifications: from mechanisms to functional consequences

Anthony R Cyr and Frederick E Domann
Antioxidants & redox signaling, Vol.15(2), pp.551-589
07/15/2011
DOI: 10.1089/ars.2010.3492
PMCID: PMC3118659
PMID: 20919933
url
https://doi.org/10.1089/ars.2010.3492View
Published (Version of record) Open Access

Abstract

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.
Animals Acetylation Oxidation-Reduction Methylation Epigenesis, Genetic Humans

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