Enhancers are a class of gene activators which increase the efficiency of transcription of genes under the control of a particular promoter. Unlike promoters, which are situated immediately upstream from the transcription site for a particular cluster of genes and are typically about 100 base pairs in length, enhancers can be situated either upstream or downstream from the RNA start site, can exist in either orientation in the DNA, are typically 50-100 base pairs in length, and are often repeated in tandem. These nucleotide sequences often contain, within about 100 nucleotides, a number of motifs representing binding sites for different proteins. Thus, several cellular or viral site-specific DNA-btttding proteins (transcription factors, sometimes known as Iransactivatmg proteins) may cluster together along a given enhancer, thereby bringing about, in a fashion that is not yet entirely clear, augmentation of binding of DNA-dependent RNA polymerase If to the promoter. Alternatively, viral or cellular proteins can interact not with the enhancer sequence itself, but with an inactive transcription factor, thus activating it. Since many of the transcription factors affecting particular enhancer sequences in viral genomes as well as cellular genomes are restricted to particular cells, tissues, or host species, they can determine the tropism of viruses.
Enhancer regions have been defined in the genomes of retroviruses, several herpesviruses, and hepatitis B virus, and in all cases they appear to influence the tropism of the relevant viruses by regulating the expression of viral genes in specific types of cells. The DNA of a dermatotropic type of papillomavirus contains an enhancer that is specifically active only in ker-atinocytes, indeed only in a subset of these cells. Further evidence for the tissue specificity of papovavirus enhancers comes from studies of transgenic mice containing the early gene region of JC polyomavirus, a common human virus which very occasionally causes a neurologic disease, progressive multifocal leukoencephalopathy; the offspring of transgenic mice bearing early genes from the JC virus develop a neurologic disease characterized pathologically by dysfunction of myelin-producing oligodendroglia, which mimics the naturally occurring disease.
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