Insulator (genetics)

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

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 topologically associating 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] Insulated neighborhoods formed by physical interaction between two CTCF-bound DNA loci contain the interactions between enhancers and their target genes.[5]

Mechanism of action[edit]

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.[6] Insulators may promote the formation of DNA loops that prevent the promoter-enhancer loops from forming.[7]

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

References[edit]

  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 139905Freely accessible. 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 3040116Freely accessible. PMID 19563753. 
  5. ^ Dowen, JM; Fan, ZP; Hnisz, D; Ren, G; Abraham, BJ; Zhang, LN; Weintraub, AS; Schuijers, J; Lee, TI; Zhao, K; Young, RA (9 October 2014). "Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes.". Cell. 159 (2): 374–87. doi:10.1016/j.cell.2014.09.030. PMC 4197132Freely accessible. PMID 25303531. 
  6. ^ 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 3372860Freely accessible. PMID 22682246. 
  7. ^ Gaszner, M; Felsenfeld, G (2006). "Insulators: Exploiting transcriptional and epigenetic mechanisms". Nature Reviews Genetics. 7 (9): 703–13. doi:10.1038/nrg1925. PMID 16909129.