Abstract
In eukaryotes, DNA is packed inside the cell nucleus in the form of chromatin, which consists of DNA, proteins such as histones, and RNA. Euchromatin, which is permissive for transcription, is spatially organized into transcriptionally inactive domains interspersed with pockets of transcriptional activity. While transcription and RNA have been implicated in euchromatin organization, it remains unclear how their interplay forms and maintains transcription pockets. Here we combine theory and experiment to analyze the dynamics of euchromatin organization as pluripotent zebrafish cells exit mitosis and begin transcription. We show that accumulation of RNA induces formation of transcription pockets which displace transcriptionally inactive chromatin. We propose that the accumulating RNA recruits RNA-binding proteins that together tend to separate from transcriptionally inactive euchromatin. Full phase separation is prevented because RNA remains tethered to transcribed euchromatin through RNA polymerases. Instead, smaller scale microphases emerge that do not grow further and form the typical pattern of euchromatin organization.
Highlights
In eukaryotes, DNA is packed inside the cell nucleus in the form of chromatin, which consists of DNA, proteins such as histones, and RNA
We conclude that the formation of transcription pockets is driven by the accumulation of RNA–RNA-binding proteins (RBPs) complexes, which displace transcriptionally inactive euchromatin
We propose that the coalescence of these pockets into large-scale phase-separated domains is prevented by the tethering of RNA transcripts to transcriptionally active euchromatin via RNA polymerase II, resulting in a pattern of microphase domains
Summary
DNA is packed inside the cell nucleus in the form of chromatin, which consists of DNA, proteins such as histones, and RNA. Euchromatin, which is permissive for transcription, is spatially organized into transcriptionally inactive domains interspersed with pockets of transcriptional activity. We propose that the accumulating RNA recruits RNA-binding proteins that together tend to separate from transcriptionally inactive euchromatin. Euchromatin itself is organized into transcriptionally inactive domains interspersed with pockets of transcriptional activity[2,5,6,7]. It has recently been shown that heterochromatin segregates from euchromatin via the physical process of phase separation[15,16,17], it remains unclear how the interspersed pattern that is characteristic of the internal organization of euchromatin is established and maintained. Physical mechanisms that could be applied to the organization of euchromatin have been proposed It has been suggested, for example, that nuclear bodies, including those formed from RNA and RNA-binding proteins (RBPs), can displace transcriptionally inactive chromatin[18]. Transcription sites establish pockets by displacing nontranscribed euchromatin and act as macromolecular amphiphiles that stabilize these pockets in a microphaseseparated configuration
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