Transcription organizes euchromatin via microphase separation

Lennart Hilbert, Yuko Sato, Ksenia Kuznetsova, Tommaso Bianucci, Hiroshi Kimura, Frank Jülicher, Alf Honigmann, Vasily Zaburdaev and Nadine L. Vastenhouw ()
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Lennart Hilbert: Center for Systems Biology Dresden
Yuko Sato: Tokyo Institute of Technology
Ksenia Kuznetsova: Max Planck Institute of Molecular Cell Biology and Genetics
Tommaso Bianucci: Max Planck Institute of Molecular Cell Biology and Genetics
Hiroshi Kimura: Tokyo Institute of Technology
Frank Jülicher: Center for Systems Biology Dresden
Alf Honigmann: Max Planck Institute of Molecular Cell Biology and Genetics
Vasily Zaburdaev: Center for Systems Biology Dresden
Nadine L. Vastenhouw: Max Planck Institute of Molecular Cell Biology and Genetics

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21589-3

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