31.1 Many DNA-Binding Proteins Recognize Specific DNA Sequences

The regulation of gene expression depends on the interplay between specific sequences within the genome and proteins that bind specifically to these sites. Specific DNA-binding proteins recognize regulatory sites that usually lie adjacent to the genes whose transcription is regulated by these proteins. The proteins of the largest family contain a helix-turn-helix motif. The first helix of this motif inserts into the major groove of DNA and makes specific hydrogen-bonding and other contacts with the edges of the base pairs.

31.2 Prokaryotic DNA-Binding Proteins Bind Specifically to Regulatory Sites in Operons

In prokaryotes, many genes are clustered into operons, which are units of coordinated genetic expression. An operon consists of control sites (an operator and a promoter) and a set of structural genes. In addition, regulator genes encode proteins that interact with the operator and promoter sites to stimulate or inhibit transcription. The treatment of E. coli with lactose induces an increase in the production of β-galactosidase and two additional proteins that are encoded in the lactose operon. In the absence of lactose or a similar galactoside inducer, the lac repressor protein binds to an operator site on the DNA and blocks transcription. The binding of allolactose, a derivative of lactose, to the lac repressor induces a conformational change that leads to dissociation from DNA. RNA polymerase can then move through the operator to transcribe the lac operon.

Some proteins activate transcription by directly contacting RNA polymerase. For example, cyclic AMP stimulates the transcription of many catabolic operons by binding to the catabolite activator protein. The binding of the cAMP–CAP complex to a specific site in the promoter region of an inducible catabolic operon enhances the binding of RNA polymerase and the initiation of transcription.

31.3 Regulatory Circuits Can Result in Switching Between Patterns of Gene Expression

The study of bacterial viruses, particularly bacteriophage λ, has revealed key aspects of gene-regulatory networks. Bacteriophage λ can develop by either a lytic or a lysogenic pathway. A key regulatory protein, the λ repressor, regulates its own expression, promoting transcription of the gene that encodes the repressor when repressor levels are low and blocking transcription of the gene when levels are high. This behavior depends on the λ right operator, which includes three sites to which λ repressor dimers can bind. Cooperative binding of the λ repressor to two of the sites stabilizes the state in which two λ repressor dimers are bound. The Cro protein binds to the same sites as does the λ repressor, but with reversed affinities. When Cro is present at sufficient concentrations, it blocks the transcription of the gene for the λ repressor while allowing the transcription of its own gene. Thus, these two proteins and the operator form a genetic switch that can exist in either of two states.

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Some prokaryotic species participate in quorum sensing. This process includes the release of chemicals called autoinducers into the medium surrounding the cells. These autoinducers are often, but not always, acyl homoserine lactones. Autoinducers are taken up by surrounding cells. When the autoinducer concentration reaches an appropriate level, it is bound by receptor proteins that activate the expression of genes, including those that promote the synthesis of more autoinducer. These chemically mediated social interactions allow these prokaryotes to change their gene-expression patterns in response to the number of other cells in their environments. Biofilms are complex communities of prokaryotes that are promoted by quorum-sensing mechanisms.

31.4 Gene Expression Can Be Controlled at Posttranscriptional Levels

Gene expression can also be regulated at the level of translation. In prokaryotes, many operons important in amino acid biosynthesis are regulated by attenuation, a process that depends on the formation of alternative structures in mRNA, one of which favors the termination of transcription. Attenuation is mediated by the translation of a leader region of mRNA. A ribosome stalled by the absence of an aminoacyl-tRNA needed to translate the leader mRNA alters the structure of mRNA, allowing RNA polymerase to transcribe the operon beyond the attenuator site.