title: Glutathione and cellular redox control in epigenetic regulation.
abstract: Epigenetics is defined as the mitotically/meiotically heritable changes in gene expression that are not due to changes in the primary DNA sequence. Over recent years, growing evidence has suggested a link between redox metabolism and the control of epigenetic mechanisms. The effect of the redox control, oxidative stress, and glutathione (GSH) on the epigenetic mechanisms occur at different levels affecting DNA methylation, miRNAs expression, and histone post-translational modifications (PTMs). Furthermore, a number of redox PTMs are being described, so enriching the histone code. Pioneer works showed how oxidized GSH inhibits the activity of S-adenosyl methionine synthetase, MAT1A, a key enzyme involved in the synthesis of S-adenosyl methionine (SAM), which is used by DNA methyltransferases (DNMTs) and histone methyltransferases (HMTs). Alteration in NAD /NADH ratio affects the activity of class III histone deacetylases (HDACs) and poly-ADP ribosyltransferases (PARPs). Furthermore, the iron redox state of the catalytic center of key enzymes influences the activity of HDACs and the activity of Tet methylcytosine dioxygenases (DNA demetylases) and JmjC histone demethylases. In this communication, we will show the intricate mechanisms that participate in the redox control of the epigenetic mechanisms. We specially focus our work in the characterization of new PTMs in histones, such as histone carbonylation and glutathionylation. Demonstrating how GSH influences the epigenetic mechanisms beyond a mere regulation of SAM levels. The mechanisms described in this communication place GSH and redox control in the landscape of the epigenetic regulation. The results shown underscore the relevant role that oxidative stress and GSH play as key factors in epigenetics, opening a new window for understating the underlying mechanisms that control cell differentiation, proliferation, development, and disease.
authors.affiliation: Center for Biomedical Network Research on Rare Diseases (CIBERer) (Medicine and Dentistry School), Physiology, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: García-Giménez
authors.affiliation: Sistemas Genómicos (Medicine and Dentistry School), Physiology, Spain.
authors.forename: José Santiago
authors.initials: JS
authors.lastname: Ibañez-Cabellos
authors.affiliation: Center for Biomedical Network Research on Rare Diseases (Medicine and Dentistry School), Physiology, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Seco-Cervera
authors.affiliation: University of Valencia (Medicine and Dentistry School), Physiology, Spain.
authors.forename: Federico V
authors.initials: FV
authors.lastname: Pallardó