The expression of a large fraction of all protein-coding genes is controlled at the transcriptional level through mechanisms involving the regulation of initiation. In eukaryotic cells, initiation of mRNA synthesis by RNA polymerase I1 is governed by DNA sequence elements comprising several functional classes. These include a core promoter element, which contains the binding site for RNA polymerase I1 and controls the location of the start site of transcription, and upstream promoter elements

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... d enhancers, which regulate the rate at which RNA polymerase I1 initiates new rounds of transcription from the core promoter. These sequence elements direct the action of two classes of transcription factors: initiation factors, which are essential for initiation and which are sufficient to direct a basal level of transcription from the core promoter, and regulatory factors, which are not required for initiation but which mediate the action of upstream promoter elements and enhancers (1-3). Analysis of a large number of eukaryotic genes has revealed structural diversity among core promoters. Whereas many are composed of a TATA box, located a short distance upstream of the cap site, and an initiator element, which encompasses the cap site, others, such as the terminal deoxynucleotidyl transferase, dihydrofolate reductase (DHFR),' and mouse ribosomal protein rpL30 promoters, lack discernible TATA boxes (4-6). To date, biochemical studies of initiation from the core region of TATA box containing promoters have progressed most rapidly. Initiation factors required for selective transcription of these promoters are being purified and characterized, and a detailed picture of the roles these factors play in assembly of an active initiation complex is emerging. This minireview will summarize recent advances in our understanding of the mechanism by which RNA polymerase I1 locates and binds selectively to the core region of TATA box containing promoters to form a complex capable of initiating RNA synthesis accurately at the cap site. RNA Polymerase 11 Studies of initiation by RNA polymerase I1 have lagged behind similar studies of bacterial polymerases. The low abundance of RNA polymerase I1 in most eukaryotic cells has made both its purification and its characterization difficult. Compared with bacterial RNA polymerases, which can be purified relatively easily in yields as high as 400 mg/kg of cell paste (7), RNA polymerase I1 is usually obtained in milligram or sub-milligram quantities from equivalent amounts of starting material (8). Until the late 1970s, the lack of DNA templates containing well defined eukaryotic promoters made biochemical studies of gene transcription by RNA polymerase I1 virtually impossible. Studies of the mechanism of selective transcription by bacterial RNA polymerases, on the other hand, were aided greatly by the availability of bacteriophage templates, such as T7 and X, which contained genetically defined promoters (9). These limitations have largely been overcome by the isolation and characterization of many eukaryotic promoters and by the development of improved methboxyl-terminal domain; AdML, adenovirus 2 major late; TF, transcription ' The abbreviations used are: DHFR, dihydrofolate reductase; CTD, carfactor; ATP+, adenosine 5'-O-(thiotriphosphate); STF, stimulatory transcription factor. ods for purifying RNA polymerase 11. Over the past several years, genes encoding many of the subunits of RNA polymerase I1 have been cloned (for reviews, see Refs.