Biomolecular condensates regulate transcription by dynamically compartmentalizing the transcription machinery. Classic models of transcription regulation focus on the recruitment and regulation of RNA polymerase II by the formation of complexes at the 1–10 nm length scale, which are driven by structured and stoichiometric interactions. These complexes are further organized into condensates at the 100–1,000 nm length scale, which are driven by dynamic multivalent interactions often involving domain–ligand pairs or intrinsically disordered regions. Regulation through condensate-mediated organization does not supersede the processes occurring at the 1–10 nm scale, but it provides regulatory mechanisms for promoting or preventing these processes in the crowded nuclear environment. Regulation of transcription by transcriptional condensates is involved in cell state transitions during animal and plant development, cell signalling and cellular responses to the environment. These condensate-mediated processes are dysregulated in developmental disorders, cancer and neurodegeneration. In this Review, we discuss the principles underlying the regulation of transcriptional condensates, their roles in physiology and their dysregulation in human diseases.

生物分子凝聚物通过动态划分转录机制来调节转录。转录调控的经典模型侧重于通过在 1-10 nm 长度尺度上形成复合物来募集和调节 RNA 聚合酶 II，这是由结构化和化学计量相互作用驱动的。这些复合物进一步组织成 100-1,000 nm 长度尺度的凝聚物，由动态多价相互作用驱动，通常涉及结构域-配体对或固有无序区域。通过凝聚态介导的组织进行调节并不能取代在 1-10 nm 尺度上发生的过程，但它为在拥挤的核环境中促进或防止这些过程提供了调节机制。转录凝聚物对转录的调节参与动植物发育过程中的细胞状态转换、细胞信号传导和细胞对环境的反应。这些凝聚物介导的过程在发育障碍、癌症和神经退行性变中失调。在这篇综述中，我们讨论了转录凝聚物调控的基本原理、它们在生理学中的作用以及它们在人类疾病中的失调。