Upstream binding factor

The rRNA promoter consists of a core element which straddles the transcriptional start site (designated as position +1) from residues -31 to +6 plus an upstream control element (UCE) about 50-80 bp in size and located about 100 bp upstream from the start site (i.e. at position -100 Fig. 4b). A transcription factor called upstream binding factor (UBF) binds both to the UCE as well as to a region next to and overlapping with the core element. Interestingly, TATA box binding protein (TBP see Topic G6), also binds to the rRNA promoter (in fact, TBP is required for initiation by all three eukaryotic RNA polymerases). The UBF and TBP transcription factors interact with each other and with RNA Pol I to form a transcription initiation complex. The RNA Pol I then transcribes... 

Fig. 2. Functional domains of human upstream binding factor.

Fig. 4. Stepwise model of transcription complex assembly. UBF, upstream binding factor. (See Color Insert.)...

Chan, E. K. L., Imai, H., Hamel, J. C., and Tan, E. M. (1991). Human autoantibody to RNA polymerase 1 transcription factor hUBF. Molecular identity of nucleolus organizer region autoantigen NOR-90 and ribosomal RNA upstream binding factor. J. Exp. Med. 173, 1239-1244. 

Anti-NOR 90 90-kDa doublet of (human) upstream binding factor (hUBF) Nucleolar organizer region (NOR)... 

Figure 37-7. Transcription elements and binding factors in the herpes simplex virus thymidine kinase ffW gene. DNA-dependent RNA polymerase II binds to the region of the TATA box (which is bound by transcription factor TEND) to form a multicomponent preinitiation complex capable of initiating transcription at a single nucleotide (+1).The frequency of this event is increased by the presence of upstream c/s-acting elements (the GC and CAAT boxes). These elements bind frans-acting transcription factors, in this example Spl and CTF (also called C/EBP, NF1, NFY). These cis elements can function independently of orientation (arrows).

In a recent study, Mandola et al. showed that the 28 bp TSER tandem repeats contain elements that bind upstream stimulating factor (USF), and also that ligand binding by USF-1 and USF-2 enhances the transcriptional activity of the TS gene (Fig. 2) (42). Electrophoretic mobility shift analysis has shown that the presence of a G-to-C single nucleotide polymorphism (SNP) within the second repeat of the 3R allele leads to decreased ability of upstream stimulatory factor (USF) to bind within the repeat and therefore sequentially result in decreased transcriptional activity of the 3R TS gene variant (42). 

RNA polymerase II transcribes messenger RNA and a few other small cellular RNAs. Class II promoters are usually defined by their sensitivity to a-amanitin. Like prokaryotic promoters, many class II promoters contain two conserved sequences, called the CAAT and TATA boxes. The TATA box is bound by a specialized transcription factor called TBP (for TATA-Binding-Factor). Binding of TBP is required for transcription, but other proteins are required to bind to the upstream (and potentially downstream) sequences that are specific to each gene. Like prokaryotic transcripts, eukaryotic RNAs are initiated with a nucleoside triphosphate. Termination of eukaryotic mRNA transcription is less well understood than is termination of prokaryotic transcription, because the 3 ends of eukaryotic mRNAs are derived by processing. See Figure 12-9. 

Transcription control factors promote or prevent RNA polymerase binding. Various trans-acting factors (proteins) bind at specific cis-acting sequences. These factors can bind upstream of the promoter. Other factors bind to enhancer sequences and the chromatin folds to allow the enhancer-binding factors to bind to the proteins at... 

Travers, M.T., Vallance, A.J., Gourlay, H.T., Gill, C.A., Klein, I., Bottema, C.B., Barber, M.C. 2001. Promoter I of the ovine acetyl-CoA carboxylase-alpha gene an E-box motif at -114 in the proximal promoter binds upstream stimulatory factor (USF)-l and USF-2 and acts as an insulin-response sequence in differentiating adipocytes. Biochem. J. 359, 273-284. 

The 5 end of MT-1 and MT-2 genes possess a TATA box, or core promoter element and numerous response elements that confer metal inducibility on the MT gene promoter (Figure 21.8). Some of these response elements such as API and AP2 in humans and in mouse, the antioxidant response element (ARE) and upstream stimulatory factor (USF) provide putative binding sites for MT transcription factors. The most common of these cis-acting proximal elements are the metal responsive elements (MREs), motifs that are conserved across vertebrate and invertebrate species. Multiple copies of MREs exist in the MT promoter region and act syner-gistically to enhance activity. 

Fatty acid synthase is transcriptionally regulated by upstream stimulatory factor and sterol regulatory element binding protein Ic (SREBP-lc), in response to feeding/insulin. 

Fig. 4.7 The FAAH promoter. Comparison of the upstream transcription factor binding sites of human and mouse FAAH promoters (not drawn to scale). Arrows indicate SP-1 binding sites on the - ( ) or + ( ) strand. An Ikaros (Ik) binding site, a cyclicAMP responsive-like element (CRE), and an estrogen-responsive element (ERE) are schematically represented in boxes...

Efficient initation of SL RNA synthesis required two sequence elements, one of which was centered approximately 50 nucleotides upstream from the transcriptional start site. Remarkably, the second sequence element was the 22nt SL sequence itself mutations in the SL sequence abolished transcription in vitro. DNase I footprinting showed that the SL sequence bound a protein factor the boundaries of the footprint exactly coincided with the SL sequence. Competition experiments indicated that binding of the factor was directly correlated with transcription (13). Further analysis has indicated that the 22nt binding factor is 60 kDa protein. It will be of considerable interest to see if this factor shares any homology with known transcription factors involved in RNA polymerase II transcription. 

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