Nuclear metabolism and the regulation of the epigenome

Cellular metabolism has emerged as a major biological node governing cellular behaviour. Metabolic pathways fuel cellular energy needs, providing basic chemical molecules to sustain cellular homeostasis, proliferation and function. Changes in nutrient consumption or availability therefore can result in complete reprogramming of cellular metabolism towards stabilizing core metabolite pools, such as ATP, S-adenosyl methionine, acetyl-CoA, NAD/NADP and α-ketoglutarate. Because these metabolites underlie a variety of essential metabolic reactions, metabolism has evolved to operate in separate subcellular compartments through diversification of metabolic enzyme complexes, oscillating metabolic activity and physical separation of metabolite pools. Given that these same core metabolites are also consumed by chromatin modifiers in the establishment of epigenetic signatures, metabolite consumption on and release from chromatin directly influence cellular metabolism and gene expression. In this Review, we highlight recent studies describing the mechanisms determining nuclear metabolism and governing the redistribution of metabolites between the nuclear and non-nuclear compartments.