When placed between an enhancer and promoter, certain DNA sequence elements 
inhibit enhancer-stimulated gene expression. The best characterized of these 
enhancer-blocking insulators, gypsy in Drosophila and the CTCF-binding element 
in vertebrates and flies, stabilize contacts between distant genomic regulatory 
sites leading to the formation of loop domains. Current results show that CTCF 
mediates long-range contacts in the mouse beta-globin locus and at the 
Igf2/H19-imprinted locus. Recently described active chromatin hubs and 
transcription factories also involve long-range interactions; it is likely that 
CTCF interferes with their formation when acting as an insulator. The properties 
of CTCF, and its newly described genomic distribution, suggest that it may play 
an important role in large-scale nuclear architecture, perhaps mediated by the 
co-factors with which it interacts in vivo.