Oxidative stress-mediated alterations in histone post-translational modifications.

Epigenetic regulation of gene expression provides a finely tuned response capacity for cells when undergoing environmental changes. However, in the context of human physiology or disease, any cellular imbalance that modulates homeostasis has the potential to trigger molecular changes that result either in physiological adaptation to a new situation or pathological conditions. These effects are partly due to alterations in the functionality of epigenetic regulators, which cause long-term and often heritable changes in cell lineages. As such, free radicals resulting from unbalanced/extended oxidative stress have been proved to act as modulators of epigenetic agents, resulting in alterations of the epigenetic landscape. In the present review we will focus on the particular effect that oxidative stress and free radicals produce in histone post-translational modifications that contribute to altering the histone code and, consequently, gene expression. The pathological consequences of the changes in this epigenetic layer of regulation of gene expression are thoroughly evidenced by data gathered in many physiological adaptive processes and in human diseases that range from age-related neurodegenerative pathologies to cancer, and that include respiratory syndromes, infertility, and systemic inflammatory conditions like sepsis.