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Concept
Insulator (genetics)
Summary
An insulator is a type of cis-regulatory element known as a long-range regulatory element. Found in multicellular eukaryotes and working over distances from the promoter element of the target gene, an insulator is typically 300 bp to 2000 bp in length. Insulators contain clustered binding sites for sequence specific DNA-binding proteins and mediate intra- and inter-chromosomal interactions.
Insulators function either as an enhancer-blocker or a barrier, or both. The mechanisms by which an insulator performs these two functions include loop formation and nucleosome modifications. There are many examples of insulators, including the CTCF insulator, the gypsy insulator, and the β-globin locus. The CTCF insulator is especially important in vertebrates, while the gypsy insulator is implicated in Drosophila. The β-globin locus was first studied in chicken and then in humans for its insulator activity, both of which utilize CTCF.
The genetic implications of insulators lie in their involvement in a mechanism of imprinting and their ability to regulate transcription. Mutations to insulators are linked to cancer as a result of cell cycle disregulation, tumourigenesis, and silencing of growth suppressors.
Insulators have two main functions:
Enhancer-blocking insulators prevent distal enhancers from acting on the promoter of neighbouring genes
Barrier insulators prevent silencing of euchromatin by the spread of neighbouring heterochromatin
While enhancer-blocking is classified as an inter-chromosomal interaction, acting as a barrier is classified as an intra-chromosomal interaction. The need for insulators arises where two adjacent genes on a chromosome have very different transcription patterns; it is critical that the inducing or repressing mechanisms of one do not interfere with the neighbouring gene. Insulators have also been found to cluster at the boundaries of topologically associating domains (TADs) and may have a role in partitioning the genome into "chromosome neighborhoods" - genomic regions within which regulation occurs.
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