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Liquid Nuclear Condensates Mechanically Sense and Restructure the Genome
Yongdae Shin1, Yi-Che Chang2, Daniel S W Lee3
1Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USA; Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 08826, South Korea.
Cell
|December 1, 2018
Summary
Biomolecular liquid phase separation in the nucleus mechanically excludes chromatin, favoring softer, euchromatic regions. Targeted DNA can be pulled together by condensate coalescence, acting as mechano-active filters.
Area of Science:
- Cellular biology
- Biophysics
- Genomics
Background:
- Intracellular organization relies on biomolecular liquid phase transitions.
- Liquid-liquid phase separation of intrinsically disordered proteins (IDPs) drives the formation of nuclear bodies.
- The mechanical influence of these condensates on chromatin structure is not well understood.
Purpose of the Study:
- To investigate how physical forces from liquid condensates restructure chromatin.
- To explore the role of mechanical properties in condensate formation and chromatin organization.
Main Methods:
- Utilized CasDrop, a CRISPR-Cas9-based optogenetic technology.
- Observed phase separation of various IDPs into liquid condensates.
- Developed a minimal physical model to explain condensate behavior.
Main Results:
- IDP condensates mechanically exclude chromatin as they grow.
- Condensates preferentially form in low-density, euchromatic regions due to stiffness sensitivity.
- Surface tension-driven coalescence can mechanically pull targeted genomic loci together.
Conclusions:
- Nuclear condensates act as mechano-active chromatin filters.
- These condensates physically manipulate chromatin by excluding non-targeted regions and concentrating targeted loci.
- Phase separation influences nuclear organization through mechanical forces on chromatin.
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