Histone oxidation as a new mechanism of metabolic control over gene expression

• Published in: Trends in genetics Vol. 40; no. 9; pp. 739 - 746
• Main Authors: Gantner, Benjamin N., Palma, Flavio R., Kayzuka, Cezar, Lacchini, Riccardo, Foltz, Daniel R., Backman, Vadim, Kelleher, Neil, Shilatifard, Ali, Bonini, Marcelo G.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2024
• Subjects: chromatin structure; cysteine oxidation; epigenetics; histone oxidation; histones; ROS; histone oxidation; histones; chromatin structure; epigenetics; ROS; cysteine oxidation
• ISSN: 0168-9525
• DOI: 10.1016/j.tig.2024.05.012

Histone oxidation provides a direct link between metabolically generated reactive oxygen species (ROS) and chromatin architectural changes enabling the activation of stress response gene expression.Histone oxidation is enacted directly by reactive metabolites and does not depend on enzyme catalysis or cofactor/substrate availability.Residues most susceptible to oxidative modification (cysteine, methionine, and tyrosine) are distinct from those modified by more traditional epigenetic writers (lysine and arginine), providing a distinct and independent pathway for metabolism-driven epigenetic regulation.
The emergence of aerobic respiration created unprecedented bioenergetic advantages, while imposing the need to protect critical genetic information from reactive byproducts of oxidative metabolism (i.e., reactive oxygen species, ROS). The evolution of histone proteins fulfilled the need to shield DNA from these potentially damaging toxins, while providing the means to compact and structure massive eukaryotic genomes. To date, several metabolism-linked histone post-translational modifications (PTMs) have been shown to regulate chromatin structure and gene expression. However, whether and how PTMs enacted by metabolically produced ROS regulate adaptive chromatin remodeling remain relatively unexplored. Here, we review novel mechanistic insights into the interactions of ROS with histones and their consequences for the control of gene expression regulation, cellular plasticity, and behavior.
The emergence of aerobic respiration created unprecedented bioenergetic advantages, while imposing the need to protect critical genetic information from reactive byproducts of oxidative metabolism (i.e., reactive oxygen species, ROS). The evolution of histone proteins fulfilled the need to shield DNA from these potentially damaging toxins, while providing the means to compact and structure massive eukaryotic genomes. To date, several metabolism-linked histone post-translational modifications (PTMs) have been shown to regulate chromatin structure and gene expression. However, whether and how PTMs enacted by metabolically produced ROS regulate adaptive chromatin remodeling remain relatively unexplored. Here, we review novel mechanistic insights into the interactions of ROS with histones and their consequences for the control of gene expression regulation, cellular plasticity, and behavior.