ATP, Mg2+, Nuclear Phase Separation, and Genome Accessibility

Misregulation of the processes controlling eukaryotic gene expression can result in disease. Gene expression is influenced by the surrounding chromatin; hence the nuclear environment is also of vital importance. Recently, understanding of chromatin hierarchical folding has increased together with the discovery of membrane-less organelles which are distinct, dynamic liquid droplets that merge and expand within the nucleus. These ‘sieve’-like regions may compartmentalize and separate functionally distinct regions of chromatin. This article aims to discuss recent studies on nuclear phase within the context of poly(ADP-ribose), ATP, and Mg2+ levels, and we propose a combinatorial complex role for these molecules in phase separation and genome regulation. We also discuss the implications of this process for gene regulation and discuss possible strategies to test this. Membrane-less organelles within the eukaryotic nucleus form distinct, dynamic, and functional compartments.The process of liquid phase separation generates these compartments.Chromatin and hence the genes contained within can be separated within these 'sieve-like' compartments to fulfill specific biological roles response to external stimuli.In addition to a concentration of proteins within these regions, ATP and Mg2+ may also concentrate within these droplets.Levels of ATP and Mg2+ may regulate the generation, maintenance, and dissolution of dynamic phase separation within the nucleus.