Heterogeneous flexibility can contribute to chromatin segregation in the cell nucleus

Martin Girard, Monica Olvera De La Cruz, John F. Marko, Aykut Erbaş

Research output: Contribution to journalArticlepeer-review

Abstract

The highly and slightly condensed forms of chromatin, heterochromatin and euchromatin, respectively, segregate in the cell nucleus. Heterochromatin is more abundant in the nucleus periphery. Here we study the mechanism of heterochromatin segregation by modeling interphase chromosomes as diblock ring copolymers confined in a rigid spherical shell using molecular dynamics simulations. In our model, heterochromatin and euchromatin are distinguished by their bending stiffnesses only, while an interaction potential between the spherical shell and chromatin is used to model lamin-associated proteins. Our simulations indicate that in the absence of attractive interactions between the nuclear shell and the chromatin, most heterochromatin segregates towards the nuclear interior due to the depletion of less flexible heterochromatin segments from the nuclear periphery. This inverted chromatin distribution,which is opposite to the conventional case with heterochromatin dominating at the periphery, is in accord with experimental observations in rod cells. This "inversion"is also found to be independent of the heterochromatin concentration and chromosome number. The chromatin distribution at the periphery found in vivo can be recovered by further increasing the bending stiffness of heterochromatin segments or by turning on attractive interactions between the nuclear shell and heterochromatin. Our results indicate that the bending stiffness of chromatin could be a contributor to chromosome organization along with differential effects of HP1α-driven phase segregation and of loop extruders and interactions with the nuclear envelope and topological constraints.

Original languageEnglish (US)
Article number014403
JournalPhysical Review E
Volume110
Issue number1
DOIs
StatePublished - Jul 2024

Funding

This work was supported by the Alexander von Humboldt-Stiftung (AvH), and the Scientific and Technological Research Council of Turkey (TUBITAK) via Grant No. 122F309. We acknowledge computing resources from the Max-Planck Computational and Data Facilities (MPCDF). Work at NU was supported by NIH Grant No. R01-GM105847, subcontract to the University of Massachusetts under NIH Grant No. UM1-HG011536, and by the U.S. Department of Energy (DOE), Office of Basic Energy Sciences under Contract No. DE-FG02-08ER46539.

ASJC Scopus subject areas

  • Statistical and Nonlinear Physics
  • Statistics and Probability
  • Condensed Matter Physics

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