Enhancers and Silencers

Transcription-coupled repair proteins from XP family  

Assessment of the obstruction by TFIIH, unwinding of the DNA by helicase activity of TFIIH, and recruitment of appropriate repair enzymes 

If ultraviolet photoproduct, recruitment of XP family repair enzymes and other factors for nucleotide excision repair 

If oxidized base, recruitment of specific glycosylases and other factors for base excision repair 

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A third class of sequence elements can either increase or decrease the rate of transcription initiation of eukaryotic genes. These elements are called either enhancers or repressors (or silencers), depending on which effect they have. They have been found in a variety of locations both upstream and downstream of the transcription start site and even within the transcribed portions of some genes. In contrast to proximal and upstream promoter elements, enhancers and silencers can exert their effects when located hundreds or even thousands of bases away from transcription units located on the same chromosome. Surprisingly, enhancers and silencers can function in an orientation-independent fashion. Literally hundreds of these elements have been described. In some cases, the sequence requirements for binding are rigidly constrained in others, considerable sequence variation is... 

Goren A, Ram O, Amit M, Keren H, Lev-Maor G et til (2006) Comparative analysis identifies exonic spUdng regulatoiy sequences - The complex definition of enhancers and silencers. Mol Cell 22 769-781... 

Enhancers and silencers are DNA sequences usually found upstream of promoters that stimulate or reduce transcription, respectively. These sequences bind to specific proteins called transcription factors. 

Pol II promoters have four elements (Figure 11.18). The first includes a variety of upstream elements, which act as enhancers and silencers. Specific binding proteins either activate transcription above basal levels, in the case of enhancers, or suppress it, in the case of silencers. Two common elements that are close to the core promoter are the GC box (-40), which has a consensus sequence of GGGGGG, and the GAAT box (extending to -110), which has a consensus sequence of GGGGAATGT. 

Less is known about elongation and termination in eukaryotes than in prokaryotes. Most of the research efforts have focused on the preinitiation complex and on the regulation by enhancers and silencers. As shown in Figure 11.19, the phosphorylated Pol II synthesizes RNA and leaves the promoter region behind. At the same time, the GTFs either are left at the promoter or dissociate from Pol II. 

As seen in prokaryotic transcription, enhancers and silencers are regulatory sequences that augment or diminish transcription, respectively. They can be upstream or downstream from the transcription initiator, and their orientation doesn t matter. They act through the intermediary of a gene-specific transcription-factor protein. As shown in Figure 11.21, the DNA must loop back so that the enhancer element and its associated transcription factor can contact the preinitiation complex. How this looping enhances transcription is stUl unknown. 

The use of enhancers and silencers is more extensive and the promoters are more complicated. 

Reflect and Apply How do the roles of enhancers and silencers differ from each other ... 

The first component includes a variety of upstream elements, which act as enhancers and silencers. 

Burgess-Beusse, B. et al. (2002). The insulation of genes from external enhancers and silencing chromatin. Proc. Natl Acad. Sci. USA, 9(Suppl 4) 16433-16437. doi 10.1073/pnas. 162342499. PMC 139905. PMID 12154228. http // www.pubmedcentral.nih.gov/articlerender.fcgi tool=pmcentrez artid=139905... 

AFP-EIA AFP-controlled E4 and E3 Artificial a-Fetoprotein promoter with enhancer and silencer elements to negate expression in86 deleted normal hepatocytes E4 proteins enhance cell lyses... 

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