Transcriptional condensates and phase separation: condensing information across scales and mechanisms

ABSTRACT

Transcription is the fundamental process of gene expression, which in eukaryotes occurs within the complex physicochemical environment of the nucleus. Decades of research have provided extreme detail in the molecular and functional mechanisms of transcription, but the spatial and genomic organization of transcription remains mysterious. Recent discoveries show that transcriptional components can undergo phase separation and create distinct compartments inside the nucleus, providing new models through which to view the transcription process in eukaryotes. In this review, we focus on transcriptional condensates and their phase separation-like behaviors. We suggest differentiation between physical descriptions of phase separation and the complex and dynamic biomolecular assemblies required for productive gene expression, and we discuss how transcriptional condensates are central to organizing the three-dimensional genome across spatial and temporal scales. Finally, we map approaches for therapeutic manipulation of transcriptional condensates and ask what technical advances are needed to understand transcriptional condensates more completely.

KEYWORDS:

• Biomolecular condensates
• coactivators
• nuclear organization
• phase separation
• transcription

Acknowledgments

The authors have no conflicts to declare. The authors apologize to all researchers whose relevant work was not able to be included. Figures were created with BioRender.com. This work is supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R35GM142837 (D.C.) and by a National Cancer Institute training grant T32CA009110 (J.D.).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The work was supported by the National Cancer Institute [T32 CA 009110] and National Institute of General Medical Sciences [R35GM142837].