The study investigates the 3D organization of the human and mouse genomes in embryonic stem cells and terminally differentiated cell types using Hi-C technology. The researchers identify large, megabase-sized chromatin interaction domains, termed "topological domains," which are stable across different cell types and highly conserved between species. These domains correlate with regions that constrain the spread of heterochromatin and are enriched for factors such as the insulator binding protein CTCF, housekeeping genes, RNAs, and SINE retrotransposons. The boundaries of these topological domains are associated with classical insulator and barrier elements, suggesting a role in transcriptional control. The findings indicate that topological domains are a fundamental property of mammalian genomes, with potential implications for understanding genome organization and function.The study investigates the 3D organization of the human and mouse genomes in embryonic stem cells and terminally differentiated cell types using Hi-C technology. The researchers identify large, megabase-sized chromatin interaction domains, termed "topological domains," which are stable across different cell types and highly conserved between species. These domains correlate with regions that constrain the spread of heterochromatin and are enriched for factors such as the insulator binding protein CTCF, housekeeping genes, RNAs, and SINE retrotransposons. The boundaries of these topological domains are associated with classical insulator and barrier elements, suggesting a role in transcriptional control. The findings indicate that topological domains are a fundamental property of mammalian genomes, with potential implications for understanding genome organization and function.