RESUMO
YAP/TEAD signaling is essential for organismal development, cell proliferation, and cancer progression. As a transcriptional coactivator, how YAP activates its downstream target genes is incompletely understood. YAP forms biomolecular condensates in response to hyperosmotic stress, concentrating transcription-related factors to activate downstream target genes. However, whether YAP forms condensates under other signals, how YAP condensates organize and function, and how YAP condensates activate transcription in general are unknown. Here, we report that endogenous YAP forms sub-micron scale condensates in response to Hippo pathway regulation and actin cytoskeletal tension. YAP condensates are stabilized by the transcription factor TEAD1, and recruit BRD4, a coactivator that is enriched at active enhancers. Using single-particle tracking, we found that YAP condensates slowed YAP diffusion within condensate boundaries, a possible mechanism for promoting YAP target search. These results reveal that YAP condensate formation is a highly regulated process that is critical for YAP/TEAD target gene expression.
RESUMO
In recent years, it has become increasingly clear that many nuclear membrane-less compartments have liquid-like properties and may form through the physicochemical process of phase separation. In this review, we will first discuss how various nuclear compartments, such as the genome, transcription compartments, and nuclear bodies are formed through phase separation. Then, we propose that inter-compartmental communications can also be prevalent and may be mediated by inter-compartmental diffusion of macromolecules, fusion among different compartments, and transient or stable contacts among nuclear compartments. Understanding how nuclear compartments communicate with each other represents an exciting new area of research and may reveal important insights about cellular functions and uncover previously under-appreciated disease mechanisms.
