Emerging insights into transcriptional condensates

Abstract

Eukaryotic transcription, a fundamental process that governs cell-specific gene expression, has long been the subject of extensive investigations in the fields of molecular biology, biochemistry, and structural biology. Recent advances in microscopy techniques have led to a fascinating concept known as "transcriptional condensates." These dynamic assemblies are the result of a phenomenon called liquid‒liquid phase separation, which is driven by multivalent interactions between the constituent proteins in cells. The essential proteins associated with transcription are concentrated in transcriptional condensates. Recent studies have shed light on the temporal dynamics of transcriptional condensates and their potential role in enhancing the efficiency of transcription. In this article, we explore the properties of transcriptional condensates, investigate how they evolve over time, and evaluate the significant impact they have on the process of transcription. Furthermore, we highlight innovative techniques that allow us to manipulate these condensates, thus demonstrating their responsiveness to cellular signals and their connection to transcriptional bursting. As our understanding of transcriptional condensates continues to grow, they are poised to revolutionize our understanding of eukaryotic gene regulation.

Fig. 1. Schematic representation of the transcriptional condensate model.

Transcriptional condensates are thought to form around enhancer-rich regions through liquid‒liquid phase separation.

Fig. 2. Dynamic models describing the functions of transcriptional condensates.

a Schematic model for the dynamic interplay between transcriptional condensates and transcription. b Schematic model for the transition of Pol II partitioning during the process of transcription.

Fig. 3. Engineering Transcriptional Condensates for Transcription Control.

a Schematic diagram of the optogenetic control of LLPS. Blue light can activate rapid clustering of IDRs containing proteins to let their concentration surpass the critical point. b Various platforms of optogenetic tools for LLPS formation are shown. Each platform contains proteins that can interact with each other under blue light conditions, such as IDR, CIBN, or iLID. Transcription activator-linked optogenetic platforms are utilized for spatiotemporal control of gene regulation.

Fig. 4. Transcriptional Condensates in the Response to Signaling.

Diverse external signals are transmitted to transcriptional condensates through cell signaling cascades. Signal molecules are recruited to the target chromatin region to form LLPS droplets with transcription factors and RNA polymerase II. H3K27ac-modified chromatin (labeled “Ac”) provides a platform for recruiting various transcription factors via long-range clustering.