Insulator (genetics)

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

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.[1] Insulators contain clustered binding sites for sequence specific DNA-binding proteins[1] and mediate intra- and inter-chromosomal interactions.[2]

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.[3][4] 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.[5]

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.

  1. ^ a b Allison, Lizabeth A. (2012). Fundamental Molecular Biology. New Jersey: John Wiley & Sons, Inc. pp. 300–301. ISBN 9781118059814.
  2. ^ Yang, Jingping; Corces, Victor G. (2011). "Chromatin Insulators: A Role in Nuclear Organization and Gene Expression". Advances in Cancer Research. 110: 43–76. doi:10.1016/B978-0-12-386469-7.00003-7. ISBN 9780123864697. ISSN 0065-230X. PMC 3175007. PMID 21704228.
  3. ^ West, Adam G.; Gaszner, Miklos; Felsenfeld, Gary (2002-02-01). "Insulators: many functions, many mechanisms". Genes & Development. 16 (3): 271–288. doi:10.1101/gad.954702. ISSN 0890-9369. PMID 11825869.
  4. ^ Gaszner, Miklos; Felsenfeld, Gary (September 2006). "Insulators: exploiting transcriptional and epigenetic mechanisms". Nature Reviews Genetics. 7 (9): 703–713. doi:10.1038/nrg1925. ISSN 1471-0064. PMID 16909129. S2CID 31291034.
  5. ^ Wai, Albert W.K.; Gillemans, Nynke; Raguz-Bolognesi, Selina; Pruzina, Sara; Zafarana, Gaetano; Meijer, Dies; Philipsen, Sjaak; Grosveld, Frank (2003-09-01). "HS5 of the human β-globin locus control region: a developmental stage-specific border in erythroid cells". The EMBO Journal. 22 (17): 4489–4500. doi:10.1093/emboj/cdg437. ISSN 0261-4189. PMC 202379. PMID 12941700.