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 threads through the cohesin protein complex into progressively larger loops until reaching specific boundary elements. In this study, we develop an analytical theory for active loop extrusion which predicts the probability of loop formation as a nonmonotonic function and describes chromatin contact probabilities. Validation of our model using Monte Carlo and hybrid Molecular Dynamics-Monte Carlo simulations shows that our theory replicates 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 can be utilized to specifically modify chromatin contact probabilities.
The active loop extrusion hypothesis proposes that chromatin threads through the cohesin protein complex into progressively larger loops until reaching specific bound-ary elements. We build upon this hypothesis and develop an analytical theory for active loop extrusion which predicts that loop formation probability is a nonmono-tonic function of loop length and describes chromatin contact probabilities. We val-idate 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 mecha-nism 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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