Gal4 activity is regulated by the Gal80 protein. (Top) In the absence of galactose, the Gal4 protein is inactive, even though it can bind to sites upstream of the GAL1 target gene. Gal4 activity is suppressed by the binding of the Gal80 protein. (Bottom) In the presence of galactose and the Gal3 protein, Gal80 undergoes a conformational change and is released, allowing the Gal4 activation domain to activate target gene transcription.