GSE122186 Alcohol metabolism directly fuels histone acetylation in the brain [ChIP-Seq]

Contributors : Philipp Mews ; Gabor Egervari ; Raffaella Nativio ; Simone Sidoli ; Greg Donahue ; Sonia I Lombroso ; Desi C Alexander ; S L Riesche ; Elizabeth A Heller ; Eric J Nestler ; Benjamin A Garcia ; Shelley L BergerSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusIn the adult brain, epigenetic control of gene expression has important roles in the processing of neural activity. Emerging evidence suggests that epigenetic regulation is dependent on metabolic state, implicating specific metabolic factors in neural functions that drive behavior. In neurons, histone acetylation is dependent on the metabolite acetyl-CoA that is produced from acetate by chromatin-bound ACSS21. Here, using in vivo stable isotope labeling in mouse, we show that alcohol metabolism rapidly fuels histone acetylation in the brain by direct deposition of alcohol-derived acetyl groups onto histones in an ACSS2-dependent manner. A similar induction was observed with heavy labeled acetate injection in vivo. Injection of labeled alcohol into a pregnant mouse results in incorporation of labeled acetyl groups into gestating fetal brains, indicating that the acetate passes through the placenta. In isolated primary hippocampal neurons ex vivo, extracellular acetate induced learning and memory-related transcriptional programs that were sensitive to ACSS2 inhibition. Strikingly, alcohol-related associative learning requires ACSS2 in vivo. These finding...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research