Loss of CTCF loops on human interphase chromosome organization

Chromatin looping, mediated by CTCFs, is a widespread principle in chromatin folding. Despite many studies that eluciate the importance of the insulator protein CTCF and cohesin complex in regulating genome folding, how chromatin loops determine the overall genome organization is unclear. We created a Chromosome Copolymer Model (CCM) to investigate the impact of CTCF loop loss on human interphase chromatin organization. We show that chromatin folding associated with loop domains is extended with a decrease in the number of CTCF loops. Surprisingly, the degree of epigenetic compartmentalization increases. In contrast, local topological associating domain (TAD) is only affected by removal of adjacent CTCF loop. Furthermore, deletion of some CTCF loops causes abnormal contacts between certain insulated loci with adjacent TADs merging, while others do not, indicating that CTCF loop is required to form a subset of TADs. The TADs whose formations are mainly driven by underlying epigenetic states have minimal dependence on CTCF loops. Moreover, our results employing complete CTCF depletion are in good agreement with experiments, supporting that cohesin is necessary for the formation of CTCF loops.