Insulator (genetics)

[1] Insulators contain clustered binding sites for sequence specific DNA-binding proteins[1] and mediate intra- and inter-chromosomal interactions.

Mutations to insulators are linked to cancer as a result of cell cycle disregulation, tumourigenesis, and silencing of growth suppressors.

CTCF protein is known to favourably bind to unmethylated sites, so it follows that methylation of CpG islands is a point of epigenetic regulation.

Gypsy affects the expression of adjacent genes pending insertion into a new genomic location, causing mutant phenotypes that are both tissue specific and present at certain developmental stages.

cHS4 marks the border between the active euchromatin in the β-globin locus and the upstream heterochromatin region that is highly condensed and inactive.

The cHS4 insulator acts as both a barrier to chromatin-mediated silencing via heterochromatin spreading, and blocks interactions between enhancers and promoters.

Within cHS4 of the chicken β-globin locus, CTCF binds to a region (FII) that is responsible for enhancer blocking activity.

[13] When insulator sequences are located in close proximity to the promoter of a gene, it has been suggested that they might serve to stabilize enhancer-promoter interactions.

[3] Loop formation is common in eukaryotes to bring distal elements (enhancers, promoters, locus control regions) into closer proximity for interaction during transcription.

In these cases, a loss of function mutation to the CTCF insulator gene changes the expression patterns and may affect the interplay between cell growth, differentiation and apoptosis and lead to tumourigenesis or other problems.

[2] Other genes that encode cell cycle regulators include BRCA1, and p53, which are growth suppressors that are silenced in many cancer types, and whose expression is controlled by CTCF.

Loss of function of CTCF in these genes leads to the silencing of the growth suppressor and contributes to the formation of cancer.

[2] The aberrant activation of insulators can modulate the expression of cancer-related genes, including matrix metalloproteinases involved in cancer cell invasion.