RNA polymerase II transcription compartments — from factories to condensates

Transcription by RNA polymerase II is a fundamental step in gene regulation that mainly occurs in discrete nuclear foci, or transcription compartments, characterized by a high local concentration of polymerases and nascent RNA. Early studies referred to these foci as transcription factories, proposing that they harbour most transcriptional activity and all relevant protein machinery to produce mature RNAs. However, this model of transcriptional organization has long remained controversial owing to its mechanistic uncertainties. Recently, new insights into how these foci may form are being provided by studies of phase-separated transcriptional condensates that encompass RNA polymerases, transcription factors and RNA. Advances in 3D genomics and chromatin imaging are also deepening our understanding of how transcription compartments might facilitate communication between cis-regulatory elements in 3D nuclear space. In this Review, we contrast historical work on transcription factories with recent findings on transcriptional condensates to better understand the architecture and functional relevance of transcription compartments.