Organization and regulation of nuclear condensates by gene activity

• Published in: bioRxiv
• Main Authors: Schede, Halima H, Natarajan, Pradeep, Chakraborty, Arup K, Shrinivas, Krishna
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 19.09.2022; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: Biophysics; Condensates; Gene clusters; Gene expression; Gene flow; Genomes; Localization
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2022.09.19.508534

Condensation by phase separation has recently emerged as a mechanism underlying many nuclear compartments essential for cellular functions. Nuclear condensates enrich nucleic acids and proteins, localize to specific genomic regions, and often promote gene expression. How diverse properties characteristic of nuclear condensates are shaped by genome organization and activity is poorly understood. Here, we develop a physics-based model to interrogate this interplay between condensation, active transcription, and genome organization. We show that spatial clustering of active genes enables precise localization and de novo nucleation of condensates. We find that strong clustering and activity drives aspherical condensate morphologies. Condensates flow towards distant gene clusters and competition between multiple clusters lead to stretched morphologies and activity-dependent repositioning. Overall, our model predicts and recapitulates morphological and dynamical features of diverse nuclear condensates and offers a unified mechanistic framework to study the interplay between non-equilibrium processes, genome structure, and multicomponent condensates in cell biology. Competing Interest Statement A.K.C is a consultant (titled Academic Partner) for Flagship Pioneering, serves on the Strategic Oversight Board of its affiliated company, Apriori Bio, and is a consultant and SAB member of another affiliated company, FL72. The authors declare no other competing interests.