Theory of chromatin organization maintained by active loop extrusion

Proc Natl Acad Sci U S A. 2023 Jun 6;120(23):e2222078120. doi: 10.1073/pnas.2222078120. Epub 2023 May 30.

Abstract

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.

Keywords: chromatin organization; loop extrusion; polymer physics.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Chromatin*
  • Chromosomes* / metabolism
  • Molecular Dynamics Simulation
  • Software

Substances

  • Chromatin
  • Cell Cycle Proteins