The formation of Topologically Associating Domains (TADs) in human interphase chromosomes remains a poorly understood process. This study proposes that loop extrusion, driven by cis-acting factors like cohesins, underlies TAD formation. In this process, cohesins form larger loops but are stalled at TAD boundaries due to interactions with boundary proteins, including CTCF. Polymer simulations show that this model can produce TADs and other features observed in Hi-C data. The model explains various experimental observations, such as the preferential orientation of CTCF motifs, enrichment of architectural proteins at TAD boundaries, and boundary deletion experiments. It also predicts specific outcomes for the depletion of CTCF versus cohesin. Additionally, loop extrusion has implications for processes like enhancer-promoter interactions, orientation-specific chromosomal looping, and mitotic chromosome compaction. The study concludes that TADs may be emergent phenomena from loop extrusion, rather than distinct genomic entities.The formation of Topologically Associating Domains (TADs) in human interphase chromosomes remains a poorly understood process. This study proposes that loop extrusion, driven by cis-acting factors like cohesins, underlies TAD formation. In this process, cohesins form larger loops but are stalled at TAD boundaries due to interactions with boundary proteins, including CTCF. Polymer simulations show that this model can produce TADs and other features observed in Hi-C data. The model explains various experimental observations, such as the preferential orientation of CTCF motifs, enrichment of architectural proteins at TAD boundaries, and boundary deletion experiments. It also predicts specific outcomes for the depletion of CTCF versus cohesin. Additionally, loop extrusion has implications for processes like enhancer-promoter interactions, orientation-specific chromosomal looping, and mitotic chromosome compaction. The study concludes that TADs may be emergent phenomena from loop extrusion, rather than distinct genomic entities.