Integrator-mediated clustering of poised RNA polymerase II synchronizes histone transcription.

Dynamic clustering of transcription players, including RNA polymerase II (Pol II), is thought to rely on multivalent interactions of their intrinsically disordered regions, thereby enhancing active transcription. Using the histone locus bodies (HLBs) of Drosophila nurse cells as a model, we find that Pol II forms long-lived, transcriptionally poised clusters distinct from liquid droplets, which contain unbound and paused Pol II. Depletion of the Integrator complex endonuclease module, but not its phosphatase module or pausing factors disperses these Pol II clusters, leaving HLBs intact. Consequently, histone transcription fails to reach peak levels during S-phase and aberrantly spills over throughout the cell cycle. We propose that clustering sequesters numerous poised Pol II molecules near gene promoters to ensure synchronous and efficient gene activation at desired times.