Condensation dynamics of sticky chromatin
ORAL
Abstract
Multicellular organisms require cells to differentiate to perform specific tasks and functions even though every cell contains the information necessary to produce all cell types of that organism. Cells differentiate by regulating gene expression in various ways. One way is by forming DNA-protein condensates inside the nucleus. Certain condensates, such as heterochromatin, suppress gene expression while others, like transcription hubs, up-regulate gene expression in the surrounding nuclear region. Current biomolecular condensate models explain equilibrium properties, like size and stability, but lack dynamics. For example, rheological properties and collapse times for large lengths of chromatin remain poorly characterized or explained. To study such dynamics, we use a mixture of coarse-grained 3D Brownian dynamics and kinetic Monte-Carlo algorithms to model DNA and associated binding proteins. Our simulations reveal two ways 'sticky' filaments go from being uncondensed, to condensed at multiple locations, to having a single condensate populating the filament. The conformational path taken is determined by the protein-DNA binding kinetics, the protein density, and the filament slack. This work sheds light on DNA and chromatin fibers reorganization on time-scales physically relevant to the cell cycle and crucial for proper gene expression during events like cell division.
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Publication: Wen Yan, Saad Ansari, Adam Lamson, Matthew A Glaser, Robert Blackwell, Meredith D Betterton, Michael Shelley (2022) Toward the cellular-scale simulation of motor-driven cytoskeletal assemblies eLife 11:e74160<br><br>https://doi.org/10.7554/eLife.74160
Presenters
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Adam R Lamson
Flatiron Institute, Simons Foundation
Authors
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Adam R Lamson
Flatiron Institute, Simons Foundation
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Olga Troyanskaya
Lewis-Sigler Institute (Princeton University), Flatiron Institute (SF)
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Michael J Shelley
Courant Inst. (NYU), Flatiron Inst. (SF), Flat Iron Institute