Deciphering the mechanics of a transcriptional switch

For half a century, the regulatory mechanism of yeast GAL gene expression has been the subject of controversy. What is known: a transcriptional switch composed of three proteins (the activator, Gal4p; the inhibitor, Gal80p; and a signal transducer, Gal3p), and two small molecules (galactose and ATP), is involved in regulating expression of genes encoding the Leloir pathway enzymes, in response to yeast cells being challenged with galactose as the sole source of carbon. Previously, Gal80p was thought to shuttle between the nucleus and the cytoplasm while Gal3p was exclusively cytoplasmic. Now, Richard J. Reece and colleagues of the University of Manchester, United Kingdom, show that Gal4p exists exclusively within the nucleus of cells while both Gal80p and Gal3p are present in both nucleus and cytoplasm. ???This suggests that the mechanism by which Gal3p functions is not simply to trap Gal80p in the cytoplasm???thereby allowing transcription mediated by Gal4p to occur,??? says first author Raymond Wightman. ???Instead, the presence of galactose promotes the formation of the Gal3p-Gal80p complex in either compartment of the cell which, in turn, relieves the inhibitory effect that Gal80p exerts over Gal4p???s transcriptional activity.??? Ultimately, by extending this work and solving three-dimensional structures for each protein, the team aims to fully understand GAL gene regulation mechanics.