Isolator (genetics)
As insulators or insulator elements (engl. Insulators or elements boundary , boundary elements ) are in the genetics of eukaryotes DNA sequences referred to, the regions of the gene expression defined by different genetic control elements such as enhancer and promoter distinguished from each other and insulate it. For example, you can prevent transcription factors from activating the genes that are upstream so that they are only able to act downstream . Isolators work through DNA-binding proteins that are specific for their sequence. Two distinct features that distinguish them from enhancers are position dependence and a phenomenon called isolator bypass. In order to fulfill its function, an isolator has to be positioned between enhancer and promoter. If two insulators are located directly next to each other, their insulating properties cancel each other out (hence bypass).
Their influence on genes that are imprinted also makes them part of epigenetic regulatory mechanisms.
Isolator types
There are two types of isolators that have two different effects:
Enhancer-blocking insulators ( enhancer blocking insulators ) are DNA elements that can be placed between an enhancer and a promoter, the interaction between these two prevented. This distinguishes them from the repressors , which act on both upstream and downstream promoters. Models suggest that two isolators form loops in chromatin through associated DNA-binding factors.
Barrier isolators ( barrier insulators ), however, protect genes before the repressing effect of heterochromatin . They suppress the position effect variegation (PEV). In contrast to euchromatin, heterochromatin is a more condensed form of chromatin that is achieved through certain histone modifications . There are only a few genes in heterochromatin and these are often not strongly expressed. In the heterochromatin in plants and vertebrates, the DNA is particularly strongly methylated on CpG islands . Heterochromatin has the property of having a repressive effect on neighboring euchromatic genes. The strength of this repression can vary from cell to cell, creating a mosaic structure in the strength of expression of the affected gene. This mosaic expression is referred to as position effect variegation.
history
The properties of enhancer-blocking isolators were described on Drosophila melanogaster in the 1980s . In genetic work with the retrotransposon gypsy , the group led by Pamela Geyer and Victor Corces at Johns Hopkins University in Baltimore found that gypsy blocks the activity of enhancers that are further away.
The first isolator element in vertebrates was described in 1993 and named cHS4. It was only at this time that the term insulator became established. A zinc finger protein called CTCF (CCCTC-Binding Factor), which also plays a role in the imprinting of Igf2, binds to the sequence of cHS4 .
swell
- ↑ PK Geyer: The role of insulator elements in defining domains of gene expression. In: Curr Opin Genet Dev. 7 (2), 1997 Apr, pp. 242-248. Review.
- ↑ PK Geyer, C. Spana, VG Corces: On the molecular mechanism of gypsy-induced mutations at the yellow locus of Drosophila melanogaster. In: EMBO J . 5 (10), 1986 Oct, pp. 2657-2662. PMID 3096713
- ^ JH Chung, M. Whiteley, G. Felsenfeld: A 5 'element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila. In: Cell . 74 (3), 1993 Aug 13, pp. 505-514. PMID 8348617
literature
- M. Gaszner, G. Felsenfeld: Insulators: exploiting transcriptional and epigenetic mechanisms. In: Nat Rev Genet . 7 (9), 2006 Sep, pp. 703-713. 2006 Aug 15th Review. PMID 16909129