4.8 Article

Theory of chromatin organization maintained by active loop extrusion

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NATL ACAD SCIENCES
DOI: 10.1073/pnas.2222078120

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loop extrusion; chromatin organization; polymer physics

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The active loop extrusion hypothesis suggests that chromatin forms loops through the cohesin protein complex until reaching boundary elements. We develop an analytical theory for active loop extrusion that predicts loop formation probability and chromatin contact probabilities. Our model is validated with simulations and recapitulates experimental chromatin conformation capture data.
The active loop extrusion hypothesis proposes that chromatin threads through the cohesin protein complex into progressively larger loops until reaching specific boundary elements. We build upon this hypothesis and develop an analytical theory for active loop extrusion which predicts that loop formation probability is a nonmonotonic function of loop length and describes chromatin contact probabilities. We validate our model with Monte Carlo and hybrid Molecular Dynamics-Monte Carlo simulations and demonstrate that our theory recapitulates experimental chromatin conformation capture data. Our results support active loop extrusion as a mechanism for chromatin organization and provide an analytical description of chromatin organization that may be used to specifically modify chromatin contact probabilities.

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