Upstream elements

TBP binds to the TATA box in the minor groove of DNA (most transcription factors bind in the major groove) and causes an approximately 100-degree bend or kink of the DNA helix. This bending is thought to facilitate the interaction of TBP-associated factors with other components of the transcription initiation complex and possibly with factors bound to upstream elements. Although defined as a component of class II gene promoters, TBP, by virtue of its association with... 

Porter, S. )., and Meyer, C. J. (1994). A distal tyrosinase upstream element stimulates gene expression in neural-crest-derived melanocytes of transgenic mice position-independent and mosaic expression. Development 120 2103-2111. 

Styrikovich, M. A., et al., 1960, Effect of Upstream Elements on Critical Boiling in a Vapor Generating Pipe, USAEC Rep. AEC-tr-4740, translated from Teploenergetika 7(5) 81—87. (5)... 

The Ross LPD and LLPD static mixers are also commercially available and widely used. The Ross mixer consists of a series of semielliptical plates that are discrimi-nately positioned in a tubular housing [66]. A typical single element consists of two plates perpendicular to each other and at a specified angle, as shown in Fig. 8.36. Most Ross mixers are constructed with four support rods to provide maximum rigidity. The mixer in Fig. 8.36 shows five elements. Each element is positioned at 90° tangentially from the upstream element. 

Le, Y., Gagneten, S., Larson, T., Santha, E., Dobi, A., v. Agoston, D., and Sauer, B. (2003) Far-upstream elements are dispensable for tissue-specific proenkephalin expression using a Cre-mediated knock-in strategy. 

Paulson KE, Darnell J Jr, Rushmore T, et al. 1990. Analysis of the upstream elements of the xenobiotic compound-inducible and positionally regulated glutathione S-transferase Yagene. Mol Cell Biol 10 1841-1852. 

Steroid receptors control gene expression in target cells. An understanding of the molecular interactions between receptors and specific nuclear components is crucial for elucidating the mechanism of hormone action. Receptor binding to at least three structural elements of nuclei has been described. These include the nuclear matrix, nucleoacidic chromatin proteins (acceptor proteins), and specific DNA sequences in 5 upstream elements of hormone responsive genes. 

Neutral mixing elements can be fitted at any point in the screw configuration. They are always completely filled and must be overrun by upstream elements. 

Huth JR, Yu L, Collins I, Mack J, Mendoza R, Isaac B, Braddock DT, Muchmore SW, Comess KM, Eesik SW, Clore GM, Lev-ens D, Hajduk PJ. NMR-driven discovery of benzoylanthranilic acid inhibitors of far upstream element binding protein binding to the human oncogene c-myc promoter. J. Med. Chem. 2004 47 4851-4857. 

RNA pol I promoter consists of a 70 base pair long core element and an upstream element that is about 100 base pairs long. The core spans a segment of DNA that includes sequences that are both up and downstream of the initiation site. 

Outside the core promoter in a subset of highly expressed genes is the upstream element (also called the UP element for upstream element). This sequence is present from 40 to 60 nucleotides upstream of the transcription start site. The UP element is bound by the ol subunit of RNA polymerase and serves to increase the efficiency of transcription by creating an additional binding site for the polymerase. 

Membrane depolarization acting as an upstream element of ZP3 signaling provides a means of activating a range of voltage-dependent mechanisms. In particular, the role of sperm voltage- sensitive Ca + channels will be discussed in a later section. 

It is apparent that the upstream signals have, in some cases, been identified and the molecular mechanism by which ZP3 produces these intracellular ionic messengers is perceived with some degree of resolution. It is equally apparent that the specific components of the signaling cascade as well as their relationship to the secretory machinery are not well understood. In partieular, recent studies have characterized the upstream elements of the cascade, focusing on the mechanisms that mediate the rise in Ca +j. The next objective may be to identify the Ca +-reg-ulated downstream targets and to tie these target proteins to secretion. 

The third combination is called a composite promoter and consists of both a TATA box and an initiator. This combination can be found in several viral promoters and it has been shown that an additional upstream TF binding site can influence whether the TATA box or the initiator element will be determining the promoter properties [16]. The authors showed that upstream elements can significantly increase the efficiency of the INR in this combination while especially SP-1 sites made the TATA box almost obsolete in their example. The combination of TATA box with an INR had the general effect to induce resistance against the detrimental effects of a TFIIB mutant, which interfered with expression from TATA-only promoters. This is also an example for the more indirect effects of specific arrangements in promoters that may not be apparent unless special conditions occur. 

TATA box is the first step in the assembly of the RNA polymerase II transcription complex. The frequency of transcription initiation is often affected by binding certain transcription factors to upstream elements such as the CAAT box and the GC box. The activity of many promoters is affected by enhancers, regulatory sequences that may occur thousands of base pairs upstream or downstream of the gene they affect. (In yeast these sequences are called upstream activator sequences, or UAS.) The effects of enhancers can be complex. For example, a single gene may be controlled by the combined activities of several enhancers. Hormone response elements (Section 16.4) often act as enhancers. 

Initiation by Pol I The regulatory elements directing Pol I initiation are similarly located relative to the transcription start site in both yeast and mammals. A core element spanning the transcription start site from -40 to +5 Is essential for Pol I transcription. An additional upstream element extending from roughly -155 to -60 stimulates In vitro Pol I transcription tenfold. 

This is the most common core promoter element A common upstream element Often found in TATA-less promoter s Octl, 0ct2 contain homei> domains... 

In placenta exon I.l, an 89 kb upstream element is utilized . This is a strong promoter and involves C/EBP-P . A strong positive enhancer element between —42 and —501 is present . The possibility exists that vitamin D receptor/ RXRa heterodimers and PPAR-y may have effects . 

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. 

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

---