(A)symmetry in the allele-specific chromosomal structural dynamics during embryogenesis

Area of Science:

• Developmental Biology
• Genomics
• Molecular Biology
• Regenerative Medicine

Background:

• Embryonic stem cells are key to regenerative medicine, but their early transcriptional landscape development is unclear.
• Genome architecture significantly impacts gene expression, making chromosome structure evolution during embryogenesis critical to understand.

Purpose of the Study:

• To investigate the spatial-temporal organization of chromosomes during embryogenesis.
• To explore the differences in chromosome structure dynamics between maternal and paternal genomes.
• To link chromosome organization to gene activation and developmental transitions.

Main Methods:

• Integration of Hi-C experimental data with data-driven modeling.
• Application of non-equilibrium coarse-grained molecular dynamics simulations.
• Analysis of allele-specific chromosome organization and dynamics.

Main Results:

• Higher-order chromosome structures (compartments, TADs) form symmetrically between maternal and paternal genomes.
• Global chromosome geometry shows asymmetry: paternal genome compacts, maternal genome exhibits complex size changes.
• Allelic asymmetry is driven by long-range rearrangements, while TADs promote symmetry and correlate with zygotic genome activation.

Conclusions:

• A mechanistic framework links chromosome structure, dynamics, and function during the totipotency to pluripotency transition.
• Allelic asymmetry in global geometry contrasts with symmetry in local structures like TADs.
• Findings provide theoretical insights into early development and regenerative medicine applications.