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bioRxiv · 10.1101/2025.03.28.645915

(A)symmetry in the Allele-Specific Chromosomal Structural Dynamics during Embryogenesis

Feng, C.·Chu, X.
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Abstract

Embryonic stem cells (ESCs) lie at the heart of regenerative medicine and hold significant potential for treating various diseases. Understanding how the transcriptional landscape of ESCs is established during embryogenesis is therefore pivotal for deciphering the origins of life and advancing therapeutic strategies. Given the intrinsic connection between genome structure and function, chromosomal structural organizations during embryogenesis play a vital role in shaping gene expression patterns in ESCs. In this study, we employed a data-driven model and non-equilibrium molecular dynamics simulations to quantify large-scale chromosomal structural dynamics during embryogenesis. We focused on allelic differences and their impact on the interplay between chromosomal structure, dynamics, and function. Our results reveal that higher-order chromosomal structure, such as compartments and topologically associated domains (TADs), follow allele-symmetric developmental pathways, whereas the overall geometrical structures of chromosomes exhibit allele asymmetry, with the paternal and maternal chromosome undergoing monotonic and non-monotonic compactions, respectively. Despite these differences, the spatial distribution of chromosomal loci, particularly those rich in genes, adapts in an allele-symmetric manner. We propose that these chromosomal structural organizations during embryogenesis are intricately linked with epigenetic modifications and likely contribute to the transition from totipotency to pluripotency. Moreover, our findings suggest that allele asymmetry in chromosome structural dynamics during embryogenesis arises from long-range interactions, while short-range structures, particularly TADs, promote allele symmetry, a process associated with zygotic genome activation (ZGA). Overall, our findings provide theoretical insights into the dynamic establishment of the ESC genome during embryogenesis from the chromosomal structure perspective, and potentially lay the groundwork for further applications in the field.

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Feng, C., Chu, X.. 2025-04-02. (A)symmetry in the Allele-Specific Chromosomal Structural Dynamics during Embryogenesis. https://doi.org/10.1101/2025.03.28.645915

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