Three-Dimensional Simulation of Whole-Genome Structuring Through the Transition from Anaphase to Interphase

Area of Science:

• Genomics
• Computational Biology
• Cell Biology

Background:

• Understanding three-dimensional genome architecture is crucial for analyzing genome regulation and function.
• Simulating genome structuring throughout the cell cycle provides insights into dynamic nuclear organization.

Purpose of the Study:

• To present computational codes for simulating human genome formation during cell cycle progression (anaphase to interphase).
• To demonstrate a method for quantitatively simulating 3D genome structure and dynamics using linear chromatin annotations.

Main Methods:

• Chromosomes are represented as linear polymers annotated with the neighboring region contact index (NCI) to classify chromatin types (A/B).
• Global Hi-C data is not used as input; simulation focuses on chromatin properties and interactions.

Main Results:

• Simulated mitotic chromosomes expand heterogeneously upon entering the G1 phase.
• This expansion drives phase separation of A and B chromatin regions, forming key interphase structures.

Conclusions:

• The simulation method successfully establishes chromosome territories, compartments, and associations with nuclear structures (lamina, nucleolus).
• This protocol enables quantitative simulation of 3D genome structure and dynamics when 1D chromosomal annotation is available.