Upstream activating sequence

An upstream activating sequence or upstream activation sequence (UAS) is a cis-acting regulatory sequence. It is distinct from the promoter and increases the expression of a neighbouring gene. Due to its essential role in activating transcription, the upstream activating sequence is often considered to be analogous to the function of the enhancer in multicellular eukaryotes. Upstream activation sequences are a crucial part of induction, enhancing the expression of the protein of interest through increased transcriptional activity. The upstream activation sequence is found adjacently upstream to a minimal promoter (TATA box) and serves as a binding site for transactivators. If the transcriptional transactivator does not bind to the UAS in the proper orientation then transcription cannot begin. To further understand the function of an upstream activation sequence, it is beneficial to see its role in the cascade of events that lead to transcription activation. The pathway begins when activators bind to their target at the UAS recruiting a mediator. A TATA-binding protein subunit of a transcription factor then binds to the TATA box, recruiting additional transcription factors. The mediator then recruits RNA polymerase II to the pre-initiation complex. Once initiated, RNA polymerase II is released from the complex and transcription begins.

The property of the GAL1-GAL10 to bind the GAL4 protein is utilised in the GAL4/UAS technique for controlled gene mis-expression in Drosophila. This is the most popular form of binary expression in Drosophila melanogaster, a system which has been adapted for many uses to make Drosophila melanogaster one of the most genetically tractable multicellular organisms. In this technique, four related binding sites between the GAL10 and GAL1 loci in Saccharomyces cerevisiae serve as an Upstream Activating Sequences (UAS) element through GAL4 binding. Several studies have been conducted with Saccharomyces cerevisiae to explore the exact function of upstream activation sequences, often focusing on the aforementioned GAL1-GAL10 intergenic region [1].

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