Enhancer (genetics)

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Enhancer (engl. Enhance "amplify", dt. Rarely transcriptional enhancer known) portions with characteristic for each enhancer sequence Base in eukaryotic DNA , which as well as the silencers to the cis-elements belong. Enhancers are made up of binding sites for transcription factors and can therefore have a cell-specific effect. They influence the attachment of the transcription complex to the promoter and thus increase the transcription activity of a gene . The spatial orientation of the enhancer to the promoter (enhancer-promoter interaction) is decisive for this transcription amplification. The typical enhancer has an average length of 800 bp and can be up to several thousand bases in front of (upstream) or behind (downstream) the promoter and still be brought into close proximity to the promoter sequence through the formation of DNA loops. The histones are also involved in the formation of these structures . The structural features of DNA that are involved in the control of transcription are complex and diverse. In cells in which they are active, they are present in an open, DNAse-sensitive structure and often have other characteristic epigenetic features, such as methylation of lysine-4 and acetylation of lysine-27 in histone 3 (H3K4me1, H3K27ac) , on.

A well-studied example of the enhancer effect is the alpha globin gene locus. Further examples are the DNA rearrangement in some tumor cells or when the Ig class change of B lymphocytes . Here, DNA segments are enzymatically removed from the DNA. In this way, the enhancer 'moves' into close proximity to the promoter. The result is an increased gene transcription of an oncogene (in the case of tumor cells ) or the production of IgG (in the case of plasma cells ). Enhancers are therefore important elements for regulating gene expression .

history

An enhancer was described for the first time in 1981. It comes from the polyomavirus SV40 and contains two identical 72 bp long sections, the 72-repeat sequences ( 72 bp repeat ) hot. Each of the two sections alone already has a weakly reinforcing effect on the promoter; together they increase the activity many times over. Walter Schaffner and Peter Gruss were among the first discoverers .

See also

literature

Individual evidence

  1. ↑ J. Malin, MR Aniba, S. Hannenhalli: Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers. In: Nucleic Acids Research. 41, 2013, p. 6828, doi: 10.1093 / nar / gkt374 .
  2. ↑ D. Vernimmen: Uncovering enhancer functions using the α-globin locus. In: PLoS genetics. Volume 10, number 10, October 2014, p. E1004668, doi: 10.1371 / journal.pgen.1004668 , PMID 25330308 , PMC 4199490 (free full text) (review).
  3. ↑ AC Hayday, SD Gillies, H. Saito, C. Wood, K. Wiman, WS Hayward, S. Tonegawa: Activation of a translocated human c-myc gene by an enhancer in the immunoglobulin heavy-chain locus. In: Nature. Volume 307, Number 5949, 1984 Jan 26-Feb 1, pp. 334-340, PMID 6420706 .
  4. ↑ J. Banerji, L. Olson, W. Schaffner: A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. In: Cell. Volume 33, Number 3, July 1983, pp. 729-740, PMID 6409418 .
  5. ↑ P. Gruss, R. Dhar, G. Khoury: Simian virus 40 tandem repeated sequences as an element of the early promoter. In: Proceedings of the National Academy of Sciences . Volume 78, Number 2, February 1981, pp. 943-947, PMID 6262784 , PMC 319921 (free full text).
  6. ↑ C. Benoist, P. Chambon: In vivo sequence requirements of the SV40 early promoter region. In: Nature. Volume 290, Number 5804, March 1981, pp. 304-310, PMID 6259538 .
  7. ↑ J. Banerji, S. Rusconi, W. Schaffner: Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. In: Cell. Volume 27, Number 2 Pt 1, December 1981, pp. 299-308, PMID 6277502 .