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In genetics, an enhancer is a short region of DNA that can be bound with proteins (namely, the trans-acting factors, much like a set of transcription factors) to enhance transcription levels of genes (hence the name) in a gene cluster. Furthermore, an enhancer is a cis-acting DNA sequence(s) which can increase transcription of genes. An enhancer does not need to be particularly close to the genes it acts on, and need not be located on the same chromosome.1 In eukaryotic cells the structure of the chromatin complex of DNA is folded in a way that functionally mimics the supercoiled state characteristic of prokaryotic DNA, so that although the DNA is far from the genes in nucleotides, it is geometrically close to the promoter and gene. This allows it to interact with the general transcription factors and RNA polymerase II. An enhancer may be located upstream or downstream of the gene that it regulates. Furthermore, an enhancer does not need to be located near to the transcription initiation site to affect the transcription of a gene, as some have been found to bind several hundred thousand base pairs upstream or downstream of the start site. Enhancers do not act on the promoter region itself, but are bound by activator proteins. These activator proteins interact with the mediator complex, which recruits polymerase II and the general transcription factors which then begin transcribing the genes. Enhancers can also be found within introns. An enhancer's orientation may even be reversed without affecting its function. Additionally, an enhancer may be excised and inserted elsewhere in the chromosome, and still affect gene transcription. That is the reason that intron polymorphisms are checked though they are not transcribed and translated.
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Theories
Currently, there are two different theories on the information processing that occurs on enhancers:2
- Enhanceosomes - rely on highly cooperative, coordinated action and can be disabled by single point mutations that move or remove the binding sites of individual proteins.
- Flexible billboards - less integrative, multiple proteins independently regulate gene expression and their sum is read in by the basal transcriptional machinery
HACNS1
HACNS1 is a gene enhancer "that may have contributed to the evolution of the uniquely opposable human thumb, and possibly also modifications in the ankle or foot that allow humans to walk on two legs". Evidence to date shows that of the 110,000 gene enhancer sequences identified in the human genome, HACNS1 has undergone the most change during the evolution of humans following the split with the ancestors of chimpanzees.3
External links
References
- ^ Spilianakis CG, Lalioti MD, Town T, Lee GR, Flavell RA (2005). "Interchromosomal associations between alternatively expressed loci". Nature 435 (7042): 637–45. doi:.
- ^ Arnosti DN, Kulkarni MM (2005). "Transcriptional enhancers: Intelligent enhanceosomes or flexible billboards?". J. Cell. Biochem. 94 (5): 890–8. doi:. http://www.bch.msu.edu/faculty/arnosti/Arnosti&Kulkarni2005JCB.pdf.
- ^ HACNS1: Gene enhancer in evolution of human opposable thumb
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