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28 Mechanisms of Transcriptional Control as Revealed by Studies of Human Transcription Factor Sp1

Albert J. Courey, Robert Tjian


Specificity protein 1 (Sp1) is a promoter-selective transcription factor that binds DNA (GC boxes) and activates a wide range of vertebrate genes. Studies of Sp1 have revealed that combinations of regulatory proteins interact with promoter/enhancers and with each other to generate transcriptional specificity. The analysis of Sp1 function also provided evidence for the notion that distantly bound factors can mediate activation by direct protein:protein interactions with factors bound close to the initiation site. Studies of Sp1 have helped establish the concept that transcription factors are remarkably modular proteins with multiple structurally distinct functional domains responsible for DNA recognition (Zn fingers) and transcriptional activation (glutamine-rich domains). Recently, in vitro reconstitution experiments with Sp1 led to the discovery of coactivators, a novel class of transcription factors that are thought to mediate communication between site-specific regulatory factors and the general transcriptional machinery.

By the late 1970s, many of the principles underlying the regulation of bacterial gene expression were firmly established. In particular, it was clear that much of this regulation occurred at the level of transcriptional initiation and involved the action of sigma factors and sequence-specific DNA-binding proteins (Miller and Reznikoff 1978; Rodriguez and Chamberlin 1982; for review, see McClure 1985). These proteins were found to interact with promoter elements close to the transcriptional start site and to modulate the activity of RNA polymerase. Furthermore, biochemical and genetic analyses were beginning to illuminate the mechanisms whereby these proteins could alter the rate of transcriptional initiation.

At the same time, our understanding...

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