Decoding the organization, dynamics, and function of the 4D genome.

Understanding how complex cell-fate decisions emerge at the molecular level is a key challenge in developmental biology. Despite remarkable progress in decoding the contribution of the linear epigenome, how spatial genome architecture functionally informs changes in gene expression remains unclear. In this review, we discuss recent insights in elucidating the molecular landscape of genome folding, emphasizing the multilayered nature of the 3D genome, its importance for gene regulation, and its spatiotemporal dynamics. Finally, we discuss how these new concepts and emergent technologies will enable us to address some of the outstanding questions in development and disease.