Biomolecular Condensates and Gene Activation in Development and Disease

Abstract

Activating the right gene at the right time and place is essential for development. Emerging evidence suggests that this process is regulated by the mesoscale compartmentalization of the gene-control machinery, RNA polymerase II and its cofactors, within biomolecular condensates. Coupling gene activity to the reversible and dynamic process of condensate formation is proposed to enable the robust and precise changes in gene-regulatory programs during signaling and development. The macromolecular features that enable condensates and the regulatory pathways that control them are dysregulated in disease, highlighting their importance for normal physiology. In this review, we will discuss the role of condensates in gene activation; the multivalent features of protein, RNA, and DNA that enable reversible condensate formation; and how these processes are utilized in normal and disease biology. Understanding the regulation of condensates promises to provide novel insights into how organization of the gene-control machinery regulates development and disease.

Keywords: biomolecular condensates; gene regulation; gene regulation in development and disease; phase separation.