Enhanceosome Vertical
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An enhanceosome is a protein complex that assembles at an enhancer region on DNA and helps to regulate the expression of a target gene.


Formation

Enhancers are bound by transcription activator proteins and transcriptional regulation is typically controlled by more than one activator. Enhanceosomes are formed in special cases when these activators cooperatively bind together along the enhancer sequence to create a distinct three-dimensional structure. Each enhanceosome is unique towards its specific enhancer. This assembly is facilitated by energetically favorable protein: protein and protein: DNA interactions. Therefore, all the necessary activators need to be present for the enhanceosome to be formed and able to function.


Function

Once the enhanceosome has been formed, it recruits coactivators and general transcription factors to the
promoter region In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of i ...
of the target gene to begin transcription. The effectiveness of this is dependent on DNA conformation. As a result, the enhanceosome also recruits non histone architectural transcription factors, called high-mobility group (HMG) proteins, which are responsible for regulating
chromatin Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in r ...
structure. These factors do not bind to the enhancer, but instead are used to restructure the DNA to ensure that the genes can be accessed by the transcription factors.


Role

Most enhanceosomes have been discovered pertaining to genes requiring tight regulation, like those associated with the cells defense system.  Using more than one kind of transcriptional activator protein could help to ensure that a gene is not transcribed prematurely.  Furthermore, the use of multiple factors enables gene regulation through a combination of cellular stimuli that function through multiple signaling cascades.


Examples


INF-β

The best known example of the enhanceosome acts on the
human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
interferon-beta The type-I interferons (IFN) are cytokines which play essential roles in inflammation, immunoregulation, tumor cells recognition, and T-cell responses. In the human genome, a cluster of thirteen functional IFN genes is located at the 9p21.3 cyto ...
gene, which is upregulated in cells that are infected by
virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...
es. Three activator proteins—
NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...
, an interferon activator protein such as
IRF-3 Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor. Function IRF3 is a member of the interferon regulatory transcription factor (IRF) family. IRF3 was originally discovered as a homolog of IRF1 and IRF2. IR ...
, and the
ATF The Bureau of Alcohol, Tobacco, Firearms and Explosives (BATFE), commonly referred to as the ATF, is a domestic law enforcement agency within the United States Department of Justice. Its responsibilities include the investigation and preven ...
-2/c-Jun complex—cooperatively bind to the upstream enhancer region upon viral infection. The interaction is mediated by a fourth protein HMG-I, which assists in stabilizing the complex by promoting inter-protein interactions. The assembled enhanceosome recruits transcriptional machinery such as
RNA polymerase In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the ...
to the promoter region to initiate
gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...
.


References

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External links


Enhanceosome
Molecule of the Month (February 2010) by David Goodsell Genetics pt:Acentuassomo