Mammalian transcription factors in yeast: strangers in a familiar land

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Abstract
Yeast has proven a valuable model system to understand eukaryotic transcription mechanisms. Extending the vale of the system even further, several investigators have attempted to express mammalian transcriptional activators or repressors directly in yeast. Mammalian transcriptional activators have been tested in yeast either directly or as fusion proteins targeted to reporters by fusion to a yeast DNA-binding domain. Most mammalian activators retain function in yeast. Yeast is an ideal system to carry out structure–function analysis. In many cases, activation domains of mammalian activators have been defined in yeast. Fine-structure analysis has also been carried out, particularly with p53. Several screens have identified point mutations in p53 that alter its activation potential. When a mammalian activator is expressed in yeast and studied at a reporter where its endogenous DNA-binding sites have been inserted, structure–function analysis has been carried out both to map DNA-binding regions within the activator and to identify the ideal DNA-binding sequence. Genetic approaches have been used in yeast to identify potential co-activators for mammalian transcription factors. This has been particularly useful in the case of nuclear hormone receptors, in which both the yeast SAGA–ADA and the SWI–SNF complex among other proteins have been identified as important for activator function. Nuclear hormone receptors require binding to hormone for full activation potential. This hormone-dependent stimulation can be recapitulated in yeast, which has led investigators to map hormone-binding domains and study the efficacy of different ligands. Furthermore, regulation of activator function in yeast by phosphorylation and binding to other mammalian regulatory proteins has been studied. Transcriptional repression by mammalian proteins has also been shown in yeast, although to a lesser extent than with activators. Both Mad–Max and pRB recruit histone deacetylase activity in yeast much as they do in mammalian cells.