Characterization of the spatiotemporal properties of the chromatin is essential to gaining insights into the physical bases of gene co-expression, transcriptional regulation and epigenetic modifications. The Gaussian network model (GNM) has proven in recent work to serve as a useful tool for modeling chromatin structural dynamics, using as input high-throughput chromosome conformation capture data. We focus here on the exploration of the collective dynamics of chromosomal structures at hierarchical levels of resolution, from single gene loci to topologically associating domains or entire chromosomes. The GNM permits us to identify long-range interactions between gene loci, shedding light on the role of cross-correlations between distal regions of the chromosomes in regulating gene expression. Notably, GNM analysis performed across diverse cell lines highlights the conservation of the global/cooperative movements of the chromatin across different types of cells. Variations driven by localized couplings between genomic loci, on the other hand, underlie cell differentiation, underscoring the significance of the four-dimensional properties of the genome in defining cellular identity. Finally, we demonstrate the close relation between the cell type-dependent mobility profiles of gene loci and their gene expression patterns, providing a clear demonstration of the role of chromosomal 4D features in defining cell-specific differential expression of genes.

The genome of a eukaryotic organism is comprised of a supra-molecular complex of chromatin fibers and intricately folded three-dimensional (3D) structures. Chromosomal interactions and topological changes in response to the developmental and/or environmental stimuli affect gene expression. Chromatin architecture plays important roles in DNA replication, gene expression, and genome integrity. Higher-order chromatin organizations like chromosome territories (CTs), A/B compartments, topologically associating domains (TADs), and chromatin loops vary among cells, tissues, and species depending on the developmental stage and/or environmental conditions (4D genomics). Every chromosome occupies a separate territory in the interphase nucleus and forms the top layer of hierarchical structure (CTs) in most of the eukaryotes. While the A and B compartments are associated with active (euchromatic) and inactive (heterochromatic) chromatin, respectively, having well-defined genomic/epigenomic features, TADs are the structural units of chromatin. Chromatin architecture like TADs as well as the local interactions between promoter and regulatory elements correlates with the chromatin activity, which alters during environmental stresses due to relocalization of the architectural proteins. Moreover, chromatin looping brings the gene and regulatory elements in close proximity for interactions. The intricate relationship between nucleotide sequence and chromatin architecture requires a more comprehensive understanding to unravel the genome organization and genetic plasticity. During the last decade, advances in chromatin conformation capture techniques for unravelling 3D genome organizations have improved our understanding of genome biology. However, the recent advances, such as Hi-C and ChIA-PET, have substantially increased the resolution, throughput as well our interest in analysing genome organizations. The present review provides an overview of the historical and contemporary perspectives of chromosome conformation capture technologies, their applications in functional genomics, and the constraints in predicting 3D genome organization. We also discuss the future perspectives of understanding high-order chromatin organizations in deciphering transcriptional regulation of gene expression under environmental stress (4D genomics). These might help design the climate-smart crop to meet the ever-growing demands of food, feed, and fodder.