Afsaneh Goudarzi1, Narges Hosseinmardi2, Siamak Salami3, Fatemeh Mehdikhani3, Samira Derakhshan4, Pouyan Aminishakib4. 1. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Afsaneh.goudarzi@sbmu.ac.ir. 2. Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Department of Oral and Maxillofacial Pathology, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
AIMS: Post-translational modifications (PTMs) of histones are regulated by the availability of their respective acyl-CoAs. Among these histone PTMs, the metabolic origin of histone butyrylation (Kbu) is still poorly understood. MATERIAL AND METHODS: The impact of starvation on the levels of Kbu was determined by western blotting on histones extracted from the liver of fed and fasted C57BL/6 mice and immunohistochemistry on liver paraffin sections. KEY FINDINGS: Using animal model we provide evidence that the stimulation of ketogenesis following starvation, in addition to histone beta-hydroxybutyrylation (Kbhb), also leads to an increase in histone butyrylation (Kbu). Using an immunohistochemistry (IHC) approach we report first that hepatocytes contained butyrylated histones with important cell-to-cell heterogeneity. More importantly, our investigations based on western blotting and IHC also proposed that the basal levels of Kbu differ between male and female mice, with female mouse hepatocytes containing higher levels of butyrylated histones. Starvation enhanced solely histone Kbu levels in the liver of males but not females. SIGNIFICANCE: This is the first demonstration of a sex-dependent large-scale stimulation of histone acylation. Our data also point to different basal metabolic conditions of the male and female liver cells with a sex-dependent impact on the hepatocytes' epigenome.
AIMS: Post-translational modifications (PTMs) of histones are regulated by the availability of their respective acyl-CoAs. Among these histone PTMs, the metabolic origin of histone butyrylation (Kbu) is still poorly understood. MATERIAL AND METHODS: The impact of starvation on the levels of Kbu was determined by western blotting on histones extracted from the liver of fed and fasted C57BL/6 mice and immunohistochemistry on liver paraffin sections. KEY FINDINGS: Using animal model we provide evidence that the stimulation of ketogenesis following starvation, in addition to histone beta-hydroxybutyrylation (Kbhb), also leads to an increase in histone butyrylation (Kbu). Using an immunohistochemistry (IHC) approach we report first that hepatocytes contained butyrylated histones with important cell-to-cell heterogeneity. More importantly, our investigations based on western blotting and IHC also proposed that the basal levels of Kbu differ between male and female mice, with female mouse hepatocytes containing higher levels of butyrylated histones. Starvation enhanced solely histone Kbu levels in the liver of males but not females. SIGNIFICANCE: This is the first demonstration of a sex-dependent large-scale stimulation of histone acylation. Our data also point to different basal metabolic conditions of the male and female liver cells with a sex-dependent impact on the hepatocytes' epigenome.