Transcription organizes euchromatin via microphase separation

In eukaryotes, DNA is packed inside the cell nucleus in the form of chromatin, which consistsof DNA, proteins such as histones, and RNA. Euchromatin, which is permissive for tran-scription, is spatially organized into transcriptionally inactive domains interspersed withpockets of transcriptional activity. While transcription and RNA have been implicated ineuchromatin organization, it remains unclear how their interplay forms and maintains tran-scription pockets. Here we combine theory and experiment to analyze the dynamics ofeuchromatin organization as pluripotent zebrafish cells exit mitosis and begin transcription.We show that accumulation of RNA induces formation of transcription pockets which dis-place transcriptionally inactive chromatin. We propose that the accumulating RNA recruitsRNA-binding proteins that together tend to separate from transcriptionally inactive euchro-matin. Full phase separation is prevented because RNA remains tethered to transcribedeuchromatin through RNA polymerases. Instead, smaller scale microphases emerge that donot grow further and form the typical pattern of euchromatin organization