TADs, CGVs, and compartmentalization in genomes: Providing a new way for crop domestication and improvement.

Genetic variation underlying phenotypic diversity between wild and domesticated species has been extensively studied, the contribution of higher-order chromatin architecture to these processes remains less explored. Advances in Hi-C and related genomic technologies have revealed that plant genomes exhibit complex three-dimensional (3D) genome organization, hierarchically structured into A/B compartments, and topologically associated domains (TADs). TADs represent self-interacting genomic regions that can constrain or regulate without directly determining transcriptional outcomes. Alterations to TAD organization or boundary have been associated with changes in chromatin interactions and gene regulatory potential in specific developmental or environmental contexts. In plants, emerging evidence indicates that TAD structure can be genetically and environmentally modulated, despite the absence of canonical architectural proteins such as CTCF. Both environmental stress and genetic perturbations have been shown to remodel chromatin organization, with context-dependent changes in gene expression. Such plasticity in chromatin dynamics that contribute to adaptive responses raises a potential link between 3D genomic structure and cryptic genetic variations (CGVs). CGVs remain phenotypically silent under normal conditions but can be revealed under environmental or genetic perturbations, representing an additional layer of regulatory potential in plant genomes. Here, we propose that stress-induced chromatin organization, including changes in TAD organization and chromatin compartmentalization, may influence accessibility and expression of CGVs in a context-dependent manner. While a direct mechanistic link between TADs and CGVs remains largely unexplored. Here, we reviewed recent findings from model plants and major crops to highlight how variation in 3D genome organization can contribute to transcriptional plasticity, stress responses, and lineage-specific regulatory evolution. By integrating 3D genomics, chromatin accessibility, and multi-omics data, we outline a conceptual framework for generating hypotheses and open questions on how TAD-associated chromatin dynamics and CGVs together may shape transcriptional plasticity, stress responses, and long-term adaptive evolution in plants with implications for future crop improvement strategies.