Varying virulence: epigenetic control of expression noise and disease processes

Gene expression noise is a significant source of phenotypic heterogeneity in otherwise identical populations of cells. Phenotypic heterogeneity can cause reversible drug resistance in diseased cells, and thus a better understanding of its origins might improve treatment strategies. In eukaryotes, data strongly suggest that intrinsic noise arises from transcriptional bursts caused by slow, random transitions between inactive and active gene states that are mediated by chromatin remodeling. In this review, we consider how chromatin modifications might modulate gene expression noise and lead to phenotypic diversity in diseases as varied as viral infection and cancer. Additionally, we argue that this fundamental information can be applied to develop innovative therapies that counteract ‘pathogenic noise’ and sensitize all diseased cells to therapeutic intervention.