Regulation of Gene Expression in Eukaryotes:- The Genes of Galactose Metabolism in Yeast Are Subject to Both Positive and Negative Regulation
Some of the general principles described above can be illustrated by one well-studied eukaryotic regulatory circuit (Fig. 1). The enzymes required for the importation and metabolism of galactose in yeast are en coded by genes scattered over several chromosomes (Table 28–3). Each of the GAL genes is transcribed separately, and yeast cells have no operons like those in bacteria. However, all the GAL genes have similar promoters and are regulated coordinately by a common set of proteins. The promoters for the GAL genes consist of the TATA box and Inr sequences, as well as an upstream activator sequence (UASG) recognized by a DNA-binding transcriptional activator known as Gal4 protein (Gal4p). Regulation of gene expression by galactose entails an interplay between Gal4p and two other proteins, Gal80p and Gal3p (Fig. 1). Gal80p forms a complex with Gal4p, preventing Gal4p from functioning as an activator of the GAL promoters. When galactose is present, it binds Gal3p, which then interacts with Gal80p, allowing Gal4p to function as an activator at the various GAL promoters. Other protein complexes also have a role in activating transcription of the GAL genes. These may include the SAGA complex for histone acetylation, the SWI/SNF complex for nucleosome remodeling, and the mediator complex. Figure 2 provides an idea of the complexity of protein interactions in the overall process of transcriptional activation in eukaryotic cells.
Glucose is the preferred carbon source for yeast, as it is for bacteria. When glucose is present, most of the GALgenes are repressed—whether galactose is present or not. The GAL regulatory system described above is effectively overridden by a complex catabolite repression system that includes several proteins (not depicted in Fig. 2).
0FIGURE 1 Regulation of transcription at genes of galactose metabolism in yeast. Galactose is imported into the cell and converted to galactose 6-phosphate by a pathway involving six enzymes whose genes are scattered over three chromosomes (see Table 28–3). Tran scription of these genes is regulated by the combined actions of the proteins Gal4p, Gal80p, and Gal3p, with Gal4p playing the central role of DNA-binding transactivator. The Gal4p-Gal80p complex is in active in gene activation. Binding of galactose to Gal3p and its inter action with Gal80p produce a conformational change in Gal80p that allows Gal4p to function in transcription activation.
FIGURE 2 Protein complexes involved in transcription activation of a group of related eukaryotic genes. The GAL system illustrates the complexity of this process, but not all these protein complexes are yet known to affect GAL gene transcription. Note that many of the complexes (such as SWI/SNF, GCN5-ADA2-ADA3, and mediator) affect the transcription of many genes. The complexes assemble step wise. First the DNA-binding transactivators bind, then the additional protein complexes needed to remodel the chromatin and allow tran scription to begin.
