Transcription organizes euchromatin via microphase separation
Open Access
- 28 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 12 (1), 1-12
- https://doi.org/10.1038/s41467-021-21589-3
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. How euchromatin organisation and transcription are related is unclear. Here, the authors observe the dynamics of euchromatin organization showing that accumulating RNA recruits RNA-binding proteins that together with transcribed euchromatin separate from non-transcribed euchromatin, forming microphases.Funding Information
- Volkswagen Foundation (Life)
- Human Frontier Science Program (CDA-00060/2012)
- Max-Planck-Gesellschaft (na)
- Japan Society for the Promotion of Science London (JP15K07157, JP17KK0143)
- In addition to those mentioned above: an ELBE Postdoctoral Fellowship from the Center for Systems Biology Dresden, and the Helmholtz Program Biointerfaces in Technology and Medicine (BIFTM).
This publication has 80 references indexed in Scilit:
- Complexity of chromatin folding is captured by the strings and binders switch modelProceedings of the National Academy of Sciences of the United States of America, 2012
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- Getting RNA and Protein in PhaseCell, 2012
- Tracking epigenetic histone modifications in single cells using Fab-based live endogenous modification labelingNucleic Acids Research, 2011
- Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human GenomeScience, 2009
- Zebrafish MiR-430 Promotes Deadenylation and Clearance of Maternal mRNAsScience, 2006
- Active genes dynamically colocalize to shared sites of ongoing transcriptionNature Genetics, 2004
- Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcriptionGenes & Development, 2004
- Localisation of rapidly and slowly labelled nuclear RNA as visualized by high resolution autoradiographyExperimental Cell Research, 1971
- Fine structural organization of the interphase nucleus in some mammalian cellsJournal of Ultrastructure Research, 1969