Promoters, activator proteins, and the mechanism of transcriptional initiation in yeast
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Initiation and regulation of mRNA transcription in eukaryotes depend on several proteins in addition to RNA polymerase II. The prevailing view is that these proteins, called transcription factors, interact with the multiple sequence elements that form the eukaryotic promoter. Our knowledge of the molecular mechanisms involved in the initiation of transcription has come in part from studies on the yeast Saccharomyces cerevisiae, in which proteins that activate transcription of specific genes in vivo have been characterized both genetically and biochemically. Yeast Promoter Elements Yeast promoters are composed of upstream (UAS), TATA, and initiator (I) elements that are necessary for the regulation, amount, and accuracy of transcriptional initiation (Figure 1). Although a simple promoter could contain just one of each kind of element, most native yeast promoters are more complex. In addition, some promoters contain operator (OP) elements that are involved in the repression of transcription (Johnson and Herskowitz, Cell 42, 237247, 1985; reviewed by Brent, Cell 42, 3-4, 1985). Upstream elements are required for transcription, and they usually determine the particular regulatory properties of a given promoter (reviewed by Guarente, Cell 36, 799-800,1984). As expected, genes subject to a common control mechanism contain upstream elements that are similar in DNA sequence. Yeast upstream elements resemble mammalian enhancer sequences; they function in both orientations and at long and variable distances (up to at least 600 bp) with respect to other promoter elements and the mRNA initiation site. Unlike enhancers, they do not appear to activate transcription when located downstream from the initiation site (Guarente and Hoar, PNAS 87,7860-7864,1984; Struhl, PNAS 81,7865-7869,1984). In general, it is believed that upstream elements are DNAbinding sites for transcriptional regulatory proteins, and as will be discussed below, this has been demonstrated in several cases. However, upstream elements for several constitutively expressed genes are poly(dA-dT) homopolymer sequences, and it has been proposed that these act by excluding nucleosomes, not by binding specific proteins (Struhl, PNAS 82, 8419-8423, 1985). TATA elements (consensus sequence TATAAA) are necessary but not sufficient for transcriptional initiation of most yeast genes. The distance between yeast TATA elements and mRNA initiation sites ranges between 40-120 bp depending on the promoter; in contrast, higher eukaryotic TATA sequences are almost always located 25-30 bp away from the initiation site (Breathnach and Chambon, Ann. Rev. Biochem. 50,349383,198l). Because they are present in many different kinds of promoters, TATA elements are presumed to have a general role in the transcription process such as binding of a general transcripMinireview