Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization. Developmental enhancers and chromosome topology. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Spatial partitioning of the regulatory landscape of the X-inactivation centre. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Organization and function of the 3D genome. Aberrant disease-related gene activation is not induced by a mere loss of insulation but requires CTCF-dependent redirection of enhancer–promoter contacts.īonev, B. Thus, TAD structures provide robustness and precision but are not essential for developmental gene regulation. Gene misexpression and disease phenotypes, however, were achieved by redirecting regulatory activity through inversions and/or the repositioning of boundaries. We show that the removal of all major CTCF sites at the boundary and within the TAD resulted in a fusion of neighboring TADs, without major effects on gene expression. Here, we investigate TAD function in vivo in mouse limb buds at the Sox9– Kcnj2 locus. Genomic rearrangements of TADs have been shown to cause gene misexpression and disease, but genome-wide depletion of CTCF has no drastic effects on transcription. The genome is organized in three-dimensional units called topologically associating domains (TADs), through a process dependent on the cooperative action of cohesin and the DNA-binding factor CTCF.
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