A generative network model reveals hierarchical structural memory guiding post-mitotic 3D genome inheritance

How the three-dimensional organization of chromosomes is restored after cell division to maintain gene regulation and cell identity has yet to be fully understood. Our research aimed to determine if the structure of chromosomes during cell division contributes to this memory by keeping structural data while allowing for necessary cellular adjustments.

We introduce HiCONA, a generative Bayesian model that reconstructs the hierarchical organization of the genome and measures the impact of individual interactions through an Entropy Impact Score. HiCONA is capable of analyzing genome organization at various levels, unveiling the patterns that define chromatin architecture, regardless of the experimental method used.

We discovered specific chromatin interactions whose structural importance remained intact during cell division, outlining separate paths for post-cell-division reorganization of the genome. These interactions that persisted through mitosis are linked to active and transcriptionally active regulatory regions, indicating that they encode structural memory which can be later altered by external regulatory factors.

Our results imply that the structural information maintained on chromosomes during cell division directs the reorganization of the genome, offering a structural explanation for the inheritance of epigenetic memory and the process of post-cell-division genome inheritance.