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Nuclear bodies form via liquid-liquid phase separation, influenced by the chromatin network. This study reveals how chromatin interactions stabilize multi-droplet states in nucleoli, explaining experimental observations.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Genomics

Background:

  • Nuclear bodies are membraneless organelles formed by liquid-liquid phase separation.
  • The chromatin network's role in nuclear body stability is poorly understood.
  • Classical theories often fail to explain experimental observations of nuclear bodies.

Purpose of the Study:

  • To investigate the thermodynamics and kinetics of nucleoli formation using a human genome model.
  • To elucidate the impact of chromatin interactions on nuclear body phase separation.
  • To explain experimental observations of nucleoli stability.

Main Methods:

  • Developed a diploid human genome model.
  • Utilized chromosome conformation capture (Hi-C) data for model parameterization.
  • Performed dynamical simulations and free energy calculations.

Main Results:

  • Simulations predicted multiple nucleoli droplets with specific interactions with nucleolus-associated domains (NADs).
  • Simulated droplet dynamics, surface tension, and coalescence kinetics matched experimental nucleoli data.
  • A two-droplet state was found to be metastable, separated by an entropic barrier.

Conclusions:

  • Nucleoli-chromatin interactions promote droplet nucleation but impede coarsening.
  • The chromatin network acts as a nucleation and arrest mechanism, stabilizing multi-droplet nucleoli.
  • This mechanism may apply to other nuclear bodies, explaining their stability.