The nucleus as a dynamic metabolic compartment linking nutrients to chromatin modification

Intracellular metabolites act as powerful signalling cues to adjust cell behaviour to the nutrient environment. A variety of metabolites operate in the nucleus as substrates, co-factors, or inhibitors of chromatin-modifying enzymes and have emerged as key determinants of gene regulation. Given that cellular metabolism is highly compartmentalised, our understanding of pathways connecting nutrients to nuclear metabolites has been limited since standard metabolite analyses use whole cells.
I will discuss our recent work in which we developed rigorous approaches for subcellular metabolite analyses by liquid chromatography-mass spectrometry, with a focus on acyl-Coenzyme A thioesters (acyl-CoAs). We show that the nucleus operates as a distinct metabolic compartment and examine the dynamic relationship between nutrient availability, acyl-CoA metabolism and histone lysine modification. This work opens new avenues to investigate the metabolic-epigenetic interface and how diet affects the epigenome.