Aberrant redox biology and epigenetic reprogramming: Co-conspirators across multiple human diseases.

An epigenetic landscape encompasses a series of dynamic interconnected mechanisms working together to fashion a diverse set of phenotypes from a singular genotype. The epigenetic plasticity observed in disease and development is facilitated by enzymes that create and remove covalent modifications to DNA and histones. Several important discoveries within the past decade have revealed that epigenetic control mechanisms are subject to redox regulation and mitochondrial-to-nuclear retrograde signaling. This has led to our current understanding that the writers and erasers of the epigenome are influenced by several levels of redox and metabolic control including the bioavailability of oxygen, nutrients, and metabolite co-factors necessary for optimal enzyme activity. Thus, these enzymes perceive a cell's redox state, metabolic status, and environmental signals to influence chromatin structure and accessibility to the transcriptional apparatus. Not only are the activities of epigenetic enzymes affected by cellular redox conditions, but also, in feedback loop fashion, genes encoding antioxidant enzymes as well as prooxidant enzymes can be altered in their expression patterns by epigenetic silencing mechanisms. The altered expression of the anti- and prooxidant genes can then contribute to the onset or progression of disease. Epigenetic regulation of gene expression by the confluence of redox biology and gene-environment interactions is an active area of research and our understanding of these links continues to evolve. Given the emergent importance of crosstalk between redox biology and epigenetic regulatory mechanisms, it is timely that this issue should explore the current state of knowledge on this topic and how changes in metabolism and redox flux can result in tectonic shifts of the epigenetic landscape.