Emergent 3D genome reorganization from the stepwise assembly of transcriptional condensates

Here we show that transcriptional condensates form in a stepwise manner to enable precise three-dimensional (3D) gene control. We demonstrate this using a quintessential model of eukaryotic gene regulation—the heat shock response (HSR).

In budding yeast, the HSR transcription activator Hsf1 forms clusters upon partially dissociating from the chaperone Hsp70. Next, Hsf1 partitions the coactivator Mediator into clusters following further Hsp70 dissociation and phosphorylation. Pol II clustering constitutes the last step that drives emergent HSR gene coalescence.