Insulator (genetics)

For electrical insulator, see Insulator (Electrical).
For other uses, see Insulation (disambiguation).

An insulator is a genetic boundary element that blocks the interaction between enhancers and promoters.

It is thought that an insulator must reside between the enhancer and promoter to inhibit their subsequent interactions. Insulators therefore determine the set of genes an enhancer can influence. 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.[1] Insulators have also been found to cluster at the boundaries of topological association domains (TADs) and may have a role in partitioning the genome into "chromosome neighborhoods" - genomic regions within which regulation occurs.[2][3]

Insulator activity is thought to occur primarily through the 3D structure of DNA mediated by proteins including CTCF.[4]

Mechanism of action

Insulators are likely to function through multiple mechanisms. Many enhancers form DNA loops that put them in close physical proximity to promoter regions during transcriptional activation.[5] Insulators may promote the formation of DNA loops that prevent the promoter-enhancer loops from forming.[6]

Barrier insulators may prevent the spread of heterochromatin from a silenced gene to an actively transcribed gene.

References

  1. ↑ Burgess-Beusse B, Farrell C, Gaszner M, Litt M, Mutskov V, Recillas-Targa F, Simpson M, West A, Felsenfeld G (December 2002). "The insulation of genes from external enhancers and silencing chromatin". Proc. Natl. Acad. Sci. U.S.A. 99 Suppl 4: 16433–7. doi:10.1073/pnas.162342499. PMC 139905. PMID 12154228.
  2. ↑ Perkel J (1 June 2015). "Mapping chromosome neighborhoods". Biotechniques 58 (6): 280–284. doi:10.2144/000114296. PMID 26054763.
  3. ↑ Ong CT, Corces VG (April 2014). "CTCF: an architectural protein bridging genome topology and function". Nat Rev Genet 15 (4): 234–46. doi:10.1038/nrg3663. PMID 24614316.
  4. ↑ Phillips JE, Corces VG (June 2009). "CTCF: master weaver of the genome". Cell 137 (7): 1194–211. doi:10.1016/j.cell.2009.06.001. PMC 3040116. PMID 19563753.
  5. ↑ Deng, W; Lee, J; Wang, H; Miller, J; Reik, A; Gregory, P. D.; Dean, A; Blobel, G. A. (2012). "Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor". Cell 149 (6): 1233–44. doi:10.1016/j.cell.2012.03.051. PMC 3372860. PMID 22682246.
  6. ↑ Gaszner, M; Felsenfeld, G (2006). "Insulators: Exploiting transcriptional and epigenetic mechanisms". Nature Reviews Genetics 7 (9): 703–13. doi:10.1038/nrg1925. PMID 16909129.
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