Three-dimensional memory of nuclear organization through cell cycles

Area of Science:

• Genomics
• Cell Biology
• Computational Biology

Background:

• Genome organization is a dynamic process influenced by structural memory from mitosis.
• Understanding cell cycle-dependent genome dynamics is crucial for deciphering cellular processes.

Purpose of the Study:

• To develop and extend a whole-genome model to simulate human genome dynamics through multiple cell cycles, focusing on mitotic and cell cycle memory.
• To investigate the role of microtubule dynamics and chromosome size in metaphase chromosome arrangement.
• To analyze the persistence of structural memory and its impact on genome organization and chromatin compartmentalization across successive cell cycles.

Main Methods:

• Development of an extended whole-genome computational model incorporating the mitotic phase.
• Simulation of successive cell cycles, progressing from mitosis to interphase and back to mitosis.
• Modeling of microtubule dynamics and forces involved in chromosome assembly during metaphase.
• Analysis of chromosome positioning based on size during metaphase.
• Investigation of the persistence of the metaphase configuration into interphase and its effect on chromosome territories.
• Modeling of chromatin domain phase separation and A/B compartmentalization at the G1 phase onset.

Main Results:

• The model successfully simulates chromosome assembly into a rosette ring structure at metaphase, influenced by chromosome size.
• Structural memory of the metaphase configuration persists through mitosis and into interphase, guiding chromosome territory distribution over multiple cell cycles.
• A/B compartmentalization through chromatin domain phase separation consistently re-establishes at each G1 phase, independent of structural memory from previous cycles.

Conclusions:

• The developed genome model elucidates the interplay between chromosome dynamics, structural memory, and genome organization across cell cycles.
• Mitotic structural memory influences chromosome territory distribution, while chromatin compartmentalization is consistently re-established each cycle.
• This model provides valuable insights for analyzing cellular processes involving genome organization and inheritance of structural information.