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38 Mechanism and Regulation of Transcriptional Activation in Eukaryotes: Conserved Features from Yeasts to Humans

Leonard Guarente


The mechanism of transcriptional initiation of protein-coding genes is remarkably conserved in eukaryotic organisms ranging from yeast to humans. Yeast transcriptional activators can function in mammalian cells, and mammalian activators can work in yeast. This conservation is reflected in the common functional properties of cis-acting elements of eukaryotic promoters, the TATA box and upstream activation sites, and in the factors that bind to these sites (TFIID and transcriptional activators). Yeast TFIID, as well as certain yeast activators, has stringently conserved homologs in mammals. The major thrust of studies described in this chapter is to employ yeast genetics and biochemistry to address central questions relating to eukaryotic transcription. First, what is the mechanism by which transcriptional activators function at a distance? Recent experiments have prompted us to propose the existence of adapters that bridge the interaction between activators bound at UASs and TFIID (and the other general factors) bound at or near the TATA box. Second, how have the functional properties of a particular activator been altered over evolution? The HAP2/3/4 heteromeric complex that binds to the CCAAT box has been the focus of this study. Third, how do signal transduction pathways influence the activity of transcriptional activators? Regulation of HAP1 activity by heme and by its cognate DNA sequence provides a model to study aspects of gene control that may relate to other systems, including the steroid hormone receptors.

A central and intriguing problem in eukaryotic biology is how gene transcription can be activated by regulatory DNA sequences...

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