Physical constraints in polymer modeling of chromatin associations with the nuclear periphery at kilobase scale

Nucleus. 2021 Dec;12(1):6-20. doi: 10.1080/19491034.2020.1868105.

Abstract

Interactions of chromatin with the nuclear lamina imposes a radial genome distribution important for nuclear functions. How physical properties of chromatin affect these interactions is unclear. We used polymer simulations to model how physical parameters of chromatin affect its interaction with the lamina. Impact of polymer stiffness is greater than stretching on its configurations at the lamina; these are manifested as trains describing extended interactions, and loops describing desorbed regions . Conferring an attraction potential leads to persistent interaction and adsorption-desorption regimes manifested by fluctuations between trains and loops. These are modulated by polymer stiffness and stretching, with a dominant impact of stiffness on resulting structural configurations. We infer that flexible euchromatin is more prone to stochastic interactions with lamins than rigid heterochromatin characterizing constitutive LADs. Our models provide insights on the physical properties of chromatin as a polymer which affect the dynamics and patterns of interactions with the nuclear lamina.

Keywords: Polymer modeling; chromatin; kinetic Monte Carlo; lamin-chromatin interaction; nuclear lamina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus
  • Chromatin*
  • Euchromatin
  • Nuclear Lamina
  • Polymers*

Substances

  • Chromatin
  • Euchromatin
  • Polymers

Grant support

We thank Nolwenn Briand, past and present members of the Collas lab, and Manoel Manghi for fruitful discussions and advice. This work was funded by EU Marie Curie Scientia Fellowship FP7-PEOPLE-2013-COFUND No. 609020 (A.B.), The University of Oslo, The Norwegian Cancer Society and the Research Council of Norway.