Transcription During Hyperosmotic Nuclear Phase Separation of HL-60/S4 Cells

Live mammalian tissue culture cells exposed to hyperosmotic stress undergo rapid dehydration, cell shrinkage and increases in intracellular solute concentrations. Interphase chromatin congeals and exhibits phase separation of chromatin associated proteins. Rapidly growing myeloid leukemia (HL-60/S4) cells were exposed for 30 and 60 minutes to hyperosmotic stress (apx 600 milliOsmolar) by addition of sucrose to the cell medium. PolyA mRNA levels were elevated for several GO gene sets (e.g., replication-dependent histones; ribosomal proteins; mitochondrial enzymes; etc.) and depressed for other classes (e.g. replication-independent histones; nuclear bodies; nuclear envelope proteins; etc.). There were no obvious coordinated programs to the changes in gene expression, a condition that we call: "transcriptome disorder." We hypothesize that this disorder arises from biophysical microheterogeneity, where individual chromatin regions possess very different critical concentrations for phase separation, a property integral to modern concepts of liquid-liquid phase separation in cell biology.