Dynamic Condensates Activate Transcription Transcriptional Components Exhibit Transient Phase Separation To Drive Gene Activation

Every aspect of human function, from proper cell differentiation and development to normal cellular maintenance, requires properly timed activation of the necessary genes. This requires transcription of genomic DNA into messenger RNA (mRNA), accomplished by RNA polymerase II (RNA Pol II), which initiates transcription at gene promoters. This highly regulated process requires hundreds of proteins that must go to the promoter in a coordinated manner. Although many of these proteins are already organized into large and stable protein complexes, and so travel as a group, the process still requires coordination of many individual proteins and preformed complexes so that they are all in the same place on genomic DNA at the same time. This problem has been appreciated for years and has led to models such as “transcription factories,” where components are organized and ready to act on a gene that goes to the cellular location of the factory ( 1 ). On pages 378, 379, and 412 of this issue, Chong et al. ( 2 ), Sabari et al. ( 3 ), and Cho et al. ( 4 ), respectively, argue that special protein domains, which interact with each other to form fleeting or more persistent interactions, form biomolecular condensates that concentrate the transcription machinery. Some of these condensates might even form droplets, generating a liquid phase separated from the rest of the nucleus. Phase separation is a phenomenon familiar to anyone who has made a salad dressing: The oil and vinegar exist as two separated liquids. Phase separation in cells creates membraneless organelles that, in this case, provide the organization necessary for productive transcription ( 5 ).