polymerase y

Basal transcription apparatus

116.21 Transcriptional activator proteins bind to sites on DNA and stimulate transcription. Most act by stimulating or stabilizing the assembly of the basal transcription apparatus.

through protein coactivators. Some activators and coactiva-tors, as well as the general transcription factors, also have acteyltransferase activity and facilitate transcription further by altering chromatin structure (see earlier subsection on histone acetylation).

Transcriptional activator proteins have two distinct functions (see Figure 16.21). First, they are capable of binding DNA at a specific base sequence, usually a consensus sequence in a regulatory promoter or enhancer; for this function, most transcriptional activator proteins contain one or more of the DNA-binding motifs discussed at the beginning of this chapter. A second function is the ability to interact with other components of the transcriptional apparatus and influence the rate of transcription. Most do so by either stabilizing or stimulating the assembly of the basal transcription apparatus.

GAL4 is a transcription activator protein that regulates the transcription of several yeast genes in galactose metabolism. GAL4 contains several zinc fingers and binds to a DNA sequence called UASG (upstream activating sequence for GAL4). UASG exhibits the properties of an enhancer— a regulatory sequence that may be some distance from the regulated gene and is independent of the gene in position and orientation (see Chapter 13). When bound to UASG, GAL4 stimulates the transcription of yeast genes needed for metabolizing galactose.

A particular region of GAL4 binds another protein called GAL80, which regulates the activity of GAL4 in the presence of galactose. When galactose is absent, GAL80 binds to GAL4 (two molecules of GAL80 bind to each molecule of GAL4), preventing GAL4 from activating transcription (< Figure 16.22). When galactose is present, however, it binds to GAL80, causing a conformational change in the protein so that it can no longer bind GAL4. The GAL4 protein is then available to activate the transcription of the genes whose products metabolize galactose.

GAL4 and a number of other transcriptional activator proteins contain multiple amino acids with negative charges that form an acidic activation domain. These acidic activators stimulate transcription by enhancing the ability of TFIIB (see Chapter 13), one of the general transcription factors, to join the basal transcription apparatus. Without the activator, the binding of TFIIB is a slow process; the activator helps "recruit" TFIIB to the initiation complex, thereby stimulating the binding of RNA polymerase and the initiation of transcription. Acidic activators may also enhance other steps in the assembly of the basal transcription apparatus.

Some regulatory proteins in eukaryotic cells act as repressors, inhibiting transcription. These repressors may bind to sequences in the regulatory promoter or to distant sequences called silencers, which, like enhancers, are position and orientation independent. Unlike repressors in bacteria, most eukaryotic repressors do not directly block RNA polymerase. These repressors may compete with activators for DNA binding sites: when a site is occupied by an activa-


Absence of galactose

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