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.