An insulator or boundary element is a novel class of regulatory sequence an
d has properties consistent with a role in limiting enhancer activity; it h
elps to define the boundary between differentially regulated loci. Original
ly, an insulator was defined operationally by its ability to protect agains
t positional effects and/or to block distal enhancer activity in transgenic
assays, whereas recent experiments have focused on the role of insulators
or boundaries in their native context. Many new features have been added to
our concept of insulators, thereby revealing the complexity of their funct
ion. All these need to be accounted for by successful models. The research
of insulator elements should provide new insights into the nature of enhanc
er function and gene regulation and provide an effective tool in applied ge
ne therapy.