Upstream activator sequence

The decisive sequence of each of these UASs (upstream activating sequences) is a 5 -GATAA-3 pentanucleotide, plus the directly flanking nucleotides, shown to be essential to UAS activity [61], Several repeats of this UAS have also been detected in the 5 -proximal DNA sequences of the GAPl and PUT4 genes [45,46], but their function has not been studied as yet. 

Prelich, G. and Winston, F. (1993) Mutations that suppress the deletion of an upstream activating sequence in yeast involvement of a protein kinase and histone H3 in repressing transcription in vivo. Genetics 135, 665-676. 

Enhancers are DNA sequences that assist in the expression of a given gene and may be located several hundred or thousand base pairs away from the gene. They are also called upstream activation sequences because they exist somewhat removed from transcription start sites. Their location varies between genes. Such sequences are bidirectional, i.e., they occur in the same way in both directions. 

An increase in the basal transcription activity originating from the promoter requires regulatory DNA sequences. These sequences can be proximally or distaUy located and serve as binding sites for transcriptional activators. The cis-acting DNA elements can be found near the promoter in either orientation. They are often termed upstream activating sequences" (UAS). Regulatory sequences can also be located far from the promoter. Their effect is independent of their orientation and they are known as enhancers. 

Fig. 1.30. Structure of a typical eucaryotic transcription start site. Enhancer elements and UAS elements (UAS upstream activating sequences) are binding sites for positive and negative regulatory DNA-binding proteins. The TATA box is the binding site for the TATA box binding protein (TBP) and serves to position the RNA polymerase holoenzyme on the promoter. For promoters that do not possess a TATA box, this function is fulfilled by an initiator region.

TBP TATA box binding protein, TAF TATA box binding protein associated factor, SRB suppressor of RNA polymerase B, CTD C-terminal domain of RNA polymerase II, PC positive cofactor, NC negative cofactor, HMG high mobihty group proteins, UAS upstream activating sequence. 

Cis elements involved in transcription in yeast (a) and in vertebrates (b). Upstream activator sequences (UAS) in yeast are similar in function to upstream enhancers in vertebrates. Yeast has no parallel to downstream enhancers found in vertebrates. 

The GAL system shows both similarities and differences to typical bacterial regulatory systems. In both systems DNA-binding regulatory proteins play a major role. However, in the yeast system the binding site for the regulatory proteins is often located some distance upstream from the RNA polymerase-binding site. In yeast such distant sites required for activation are referred to as upstream activator sequences (UASs). 

Bachhawat, N., Ouyang, Q., and Henry, S.A., 1995, Functional characterization of an inositol-sensitive upstream activation sequence in yeast A c/,v-regulatory element responsible for inositol-choline mediated regulation of phospholipid biosynthesis. J. Biol. Chem. 270 25087-25095. 

Kodaki, T., Hosaka, K., Nikawa, J.-I., and Yamashita, S., 1991a, Identification of the upstream activation sequences responsible for the expression and regulation of the PEM1 and PEM2 genes encoding the enzymes of the phosphatidylethanolamine methylation pathway in Saccharomyces cerevisiae. J. Biochem. 109 276-287. 

The activities of many promoters in higher eukaryotes are greatly increased by another type of cis-acting element called an enhancer. Enhancers sequences have no promoter activity of their own yet can exert their stimulatory actions over distances of several thousand base pairs. They can be upstream, downstream, or even in the midst of a transcribed gene. Moreover, enhancers are effective when present on either DNA strand (equivalently, in either orientation). Enhancers in yeast are known as upstream activator sequences (UASs). 

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