Non-equilibrium regulation and organization of transcriptional condensates by RNA synthesis*

Precise and robust expression of genes is essential to development and cell-type specificity. Recent evidence suggests that the key transcriptional proteins phase separate to form dynamic assemblies (or condensates) at particular genomic loci. How these dynamic assemblies are regulated dynamically and spatially is largely unknown. We leverage approaches from non-equilibrium statistical physics and complex coacervates to propose a model by which RNA, the product of gene expression, regulates transcriptional condensate dynamics. We find that low amounts of RNA synthesis promote condensate formation and higher amounts, such as from high levels of gene expression, dissolve condensates - providing a dual feedback mechanism. Predictions that connect perturbations of dynamic parameters to variations in condensate size and lifetime are verified by experiments in vivo. Finally, we extend our model to explore how spatial patterns of gene expression leads to long-range information transfer between sites of RNA synthesis and transcriptional condensates and predicts various non-equilibrium morphologies that are consistent with old experimental observations.