Loss of histone macroH2A1.1 causes kidney abnormalities secondary to a change in nutrient metabolization.

ABSTRACT: Histone variants with metabolite-binding macrodomains provide a poorly understood link between chromatin composition and metabolism. To address their contribution to physiological health, we generated and analyzed mice individually lacking the histone variants macroH2A1.1, macroH2A1.2, or macroH2A2. We identified several histopathologic changes in the kidney as isoform-specific phenotype of complete macroH2A1.1 loss affecting male and female animals. Kidney alterations were barely associated with organ-intrinsic gene expression changes but strongly correlated with a systemic shift in nutrient metabolization and alterations in NAD⁺ (nicotinamide adenine dinucleotide, oxidized form) metabolism. Reduced lipid oxidation and increased glycolysis were found in male and female mice lac

SUBMITTER: Winkler R 

PROVIDER: S-EPMC12551714 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature