Chromatin insulators: a role in nuclear organization and gene expression

Chromatin insulators are DNA-protein complexes with broad functions in nuclear biology. Based on the ability of insulator proteins to interact with each other, it was originally found that insulators form loops that bring together distant regions of the genome. Data from genome-wide localization studies indicate that insulator proteins can be present in intergenic regions as well as at the 5', introns or 3' of genes, suggesting a variety of roles for insulator loops in chromosome biology. Recent results suggest that insulators mediate intra- and interchromosomal interactions to affect transcription, imprinting, and recombination. Cells have developed mechanisms to control insulator activity by recruiting specialized proteins or by covalent modification of core components. It is then possible that insulator-mediated interactions set up cell-specific blueprints of nuclear organization that may contribute to the establishment of different patterns of gene expression during cell differentiation and development. As a consequence, disruption of insulator activity could result in the development of cancer or other disease states.