A two-way relationship between histone acetylation and metabolism

A link between epigenetics and metabolism was initially recognized because the cellular metabolic state is communicated to the genome through the concentration of intermediary metabolites that are cofactors of chromatin-modifying enzymes. Recently, an additional interaction was postulated due to the capacity of the epigenome to store substantial amounts of metabolites that could become available again to cellular metabolite pools. Here, we focus on histone acetylation and review recent evidence illustrating this reciprocal relationship: in one direction, signaling-induced acetyl-coenzyme A (acetyl-CoA) changes influence histone acetylation levels to regulate genomic functions, and in the opposite direction histone acetylation acts as an acetate reservoir to directly affect downstream acetyl-CoA-mediated metabolism. This review highlights the current understanding, experimental challenges, and future perspectives of this bidirectional interplay.