Schematic of the GAL regulatory network model. A transcriptional activator protein, Gal4p, binds a consensus upstream activating sequence (UAS) in the promoter region of structural and regulatory genes promoting their expression. In the absence of galactose, however, Gal4p forms a complex with the Gal80p repressor molecule, which masks its C-terminal activation domain, preventing the recruitment of transcriptional machinery. Galactose is imported from the environment by non-specific hexose transporters, as well as by highly-specific Gal2p permeases, and activates the co-inducer Gal3p molecule or the bi-functional Gal1/3p if it is present in the network. The activated form of Gal3p (and/or Gal1/3p) can then bind and sequester Gal80p, relieving the inhibition of gene expression and permitting induction of the GAL cluster. GAL1 has a core of three UASs arranged in an in-phase helical manner. This configuration allows cooperative interactions (black connecting lines in figure) between adjacently bound activating (Gal4p) and inhibiting (Gal4p-Gal80p complex, not shown) protein pairs, which enhance gene expression or inhibition in induced or uninduced conditions respectively. The promoter region of GAL1/3 also contains this core, but, unlike GAL1, these sites are arranged in an anti-phase helical configuration which does not permit cooperative interactions. GAL3 has retained only one UAS, resulting in decreased inhibition in uninduced conditions and a relatively small induction in the presence of galactose. In addition to the changes in the number and arrangement of cis-regulatory elements, differences also exist between the intrinsic strengths of ancestral and extant promoters (see Table 4). Note that cooperative interactions between the two UASs on GAL2 are permitted , and that the 4th UAS on GAL1 (and GAL1/3) is not included in the model after indications that it may not be as important for gene expression as the other UASs .