Genomic Insulators in Transgenic Animals

Abstract

Vertebrate genomes are functionally and structurally organised as gene expression domains. These domains contain all regulatory elements required for the gene (or genes) to be expressed correctly, and include those required to shield each domain, thereby blocking any non-desirable interaction from their neighbours. These elements are known as “boundaries” or “insulators” and their function is to insulate gene expression domains in genomes allowing the protected locus to be expressed according to internal regulatory elements, without suffering from the adverse effects of flanking loci and without transmitting the effect of the internal regulatory elements beyond the protected domain. Insulators can act as “enhancer blockers”, preventing a distal enhancer from interacting with a proximal promoter, when placed in between, and/or as “barriers”, preventing chromosomal position effects associated with the genomic location. In addition, insulators are known to contribute to the chromatin and nuclear structural organization. A variety of molecular mechanisms have been associated with boundary function, probably reflecting the diversity of functional elements that can efficiently insulate genomic sequences. Insulator elements can be used in biotechnological applications, as spacers, as boundaries, and be applied to any gene expression construct to be used in gene transfer experiments (i.e. transgenesis, gene therapy), thereby preventing the inappropriate expression patterns of constructs and shielding them from neighbouring sequences surrounding the place of insertion in the host genomes.