The chapter discusses the organizational principles of 3D genome architecture, focusing on the hierarchical organization of chromosomes into large compartments called Topological Domain (TADs) and smaller compartments called compartmental domains. Recent evidence suggests that compartments are smaller than previously thought and are influenced by transcriptional or chromatin states. In vertebrates, CTCF forms loop domains through an extrusion process involving cohesin, which interacts with compartmental domains to establish the 3D organization of the genome. The continuous extrusion of chromatin by cohesin may also be responsible for enhancing interactions between enhancers and promoters and stochastic aspects of transcription. The chapter highlights the interdependence between transcription and 3D genome architecture, suggesting that both are closely linked and influence each other. It also explores the mechanisms of loop extrusion, the role of CTCF and cohesin in 3D organization, and their impact on gene regulation. The findings suggest that 3D genome organization is not just a determinant but also a consequence of its function, and that a balance between compartmental domains and CTCF loops is essential for proper chromatin organization.The chapter discusses the organizational principles of 3D genome architecture, focusing on the hierarchical organization of chromosomes into large compartments called Topological Domain (TADs) and smaller compartments called compartmental domains. Recent evidence suggests that compartments are smaller than previously thought and are influenced by transcriptional or chromatin states. In vertebrates, CTCF forms loop domains through an extrusion process involving cohesin, which interacts with compartmental domains to establish the 3D organization of the genome. The continuous extrusion of chromatin by cohesin may also be responsible for enhancing interactions between enhancers and promoters and stochastic aspects of transcription. The chapter highlights the interdependence between transcription and 3D genome architecture, suggesting that both are closely linked and influence each other. It also explores the mechanisms of loop extrusion, the role of CTCF and cohesin in 3D organization, and their impact on gene regulation. The findings suggest that 3D genome organization is not just a determinant but also a consequence of its function, and that a balance between compartmental domains and CTCF loops is essential for proper chromatin organization.