9.1 Structural and Regulatory Genes
Key Takeaways
A structural gene codes a protein used in metabolism or structure, and a regulatory gene codes a product, often a repressor, that controls other genes.
Without lactose, the lac repressor binds the operator and RNA polymerase cannot transcribe the lac structural genes lacZ, lacY, and lacA.
Allolactose inactivates the lac repressor, and high transcription also requires scarce glucose so cAMP rises and CAP-cAMP helps RNA polymerase bind the promoter.
The trp operon is repressible: it stays on when tryptophan is scarce, and abundant tryptophan acts as a corepressor so the repressor binds the operator.
Eukaryotes do not typically group metabolic genes into operons; they use transcription factors, enhancers, euchromatin versus heterochromatin, and alternative splicing.
9.1 Structural and Regulatory Genes
CLEP Biology expects a precise account of how bacteria switch genes, and of how eukaryotic cells do the same job with different DNA arrangements. A structural gene codes a protein used in metabolism or structure. A regulatory gene codes a product, often a repressor, that controls other genes. The repressor is not the enzyme of the pathway it controls. Mixing those two roles is a standard trap, especially in the lactose system, where the digestive enzyme and the repressor are different proteins coded by different genes.
Prokaryotic Operons
Promoters, Operators, and Shared Transcription
Bacteria often group the structural genes of one pathway into an operon, a DNA region transcribed from a single promoter. The promoter is where RNA polymerase binds. Next to it, the operator is the DNA site where a repressor can bind. If the repressor occupies the operator, RNA polymerase cannot transcribe the structural genes. If the operator is clear, polymerase can copy the whole set into one messenger RNA. That message is polycistronic: several polypeptides are translated from one transcript. The regulatory gene that codes the repressor usually has its own promoter. In the lactose system that gene is lacI. It is transcribed at a low steady rate, so repressor protein is present before the pathway is needed.
The Inducible lac Operon
The lac operon is inducible. Its default is off, and lactose is the cue that can turn it on. The structural genes are lacZ, lacY, and lacA. lacZ codes beta-galactosidase, which cleaves lactose into glucose and galactose. lacY codes lactose permease, which transports lactose into the cell. lacA codes thiogalactoside transacetylase. Without lactose, the lac repressor binds the operator, and RNA polymerase cannot transcribe lacZ, lacY, and lacA. The operon is off. When lactose is present, some of it is converted to allolactose. Allolactose binds the repressor and inactivates it, so the repressor leaves the operator and transcription of the three structural genes can proceed. Beta-galactosidase, not the repressor, is the enzyme that digests lactose.
Inducing the operon is not the same as transcribing it at a high rate. E. coli prefers glucose. When glucose is scarce, cyclic adenosine monophosphate (cAMP) rises and binds the catabolite activator protein (CAP), also called the cAMP receptor protein. The CAP-cAMP complex binds near the lac promoter and helps RNA polymerase bind that promoter. This help is positive control. Transcription is high only when lactose is present and glucose is scarce: allolactose has inactivated the repressor, and CAP-cAMP is helping polymerase. When glucose is abundant, cAMP stays low, CAP does not help, and lac transcription stays low even if lactose is present. Picture E. coli in a lactose-only medium. The lac genes are transcribed. Adding glucose reduces that transcription through low cAMP. The DNA did not change. The sugar signals did.
The Repressible trp Operon
The trp operon is repressible. Its structural genes code enzymes that synthesize tryptophan. When tryptophan is scarce, the operon is on, and the cell makes those tryptophan-synthesis enzymes. The trp repressor alone does not bind the operator. When tryptophan is abundant, it acts as a corepressor. The tryptophan-repressor complex binds the operator, and transcription stops. Biosynthetic operons are often repressible, because the cell should stop making a product it already has. Catabolic operons such as lac are inducible, because the cell should make breakdown proteins only when the substrate appears.
Inducible and repressible name the response to a metabolite. Negative control names a repressor that can block transcription. Both the lac operon and the trp operon use negative control. CAP-cAMP adds positive control on lac, and only when glucose is low.
| Feature | lac operon | trp operon |
|---|---|---|
| Control class | Inducible catabolic pathway under negative control, plus positive control by CAP-cAMP | Repressible biosynthetic pathway under negative control |
| Structural genes code | Lactose uptake and breakdown proteins, including beta-galactosidase from lacZ | Enzymes of tryptophan synthesis |
| Signal missing | Repressor binds the operator, so lacZ, lacY, and lacA stay off | Operon stays on, and tryptophan-synthesis enzymes are made |
| Signal abundant | Allolactose inactivates the repressor, so transcription can proceed | Tryptophan is the corepressor, the repressor binds the operator, and transcription stops |
| Glucose and cAMP | High transcription also needs scarce glucose, high cAMP, and CAP-cAMP at the promoter | The basic trp model does not use CAP-cAMP |
Warning
The lac operon is off when lactose is absent, because the repressor binds the operator. Do not call the repressor the enzyme that digests lactose. That enzyme is beta-galactosidase, the lacZ product. The regulatory gene codes the repressor that decides whether transcription starts.
Eukaryotic Gene Regulation
Separate Genes, Not a Metabolic Operon
Eukaryotes do not typically group metabolic genes into operons. A human cell does not line up every enzyme of one pathway behind a single operator. Each protein-coding gene usually has its own promoter, and genes that work in the same pathway may sit on different chromosomes. The cell can still turn related genes on together by sending the same signals to many separate genes, rather than by sharing one operator.
Transcription Factors, Enhancers, and Chromatin
Transcription factors bind specific DNA sequences and increase or decrease transcription. An enhancer is a DNA region that can raise transcription even when it lies far from the promoter. The DNA loops so proteins at the enhancer meet proteins at the promoter. A bacterial operator sits beside the promoter it controls, so this kind of distant regulation is a eukaryotic feature to remember. Chromatin packing adds another layer. DNA wound on histones may be open or closed. Euchromatin is less tightly packed and is more available for transcription. Heterochromatin is more tightly packed and is less available. A gene with an intact promoter can still be silent if it lies in heterochromatin.
Alternative Splicing
Eukaryotic pre-messenger RNA contains exons and introns. Alternative splicing joins exons in more than one pattern, so one gene can produce more than one polypeptide. Bacteria do not use splice-site choice to diversify the products of an operon. Their structural genes are separate coding regions on one polycistronic message. A CLEP item that describes two related proteins from one human primary transcript is describing alternative splicing, not a lac operon. The prokaryotic pattern in this chapter is one promoter, one operator, and a repressor that senses a metabolite. The eukaryotic pattern is transcription factors, distant enhancers, chromatin that is more or less available, and splicing after the transcript is made.
In E. coli with no lactose available, which description of the lac operon is correct?
The lac repressor binds the operator, and RNA polymerase cannot transcribe lacZ, lacY, and lacA.
CAP-cAMP binds the promoter and forces transcription of the lac structural genes even though lactose is absent.
Allolactose has already inactivated the repressor, so lacZ, lacY, and lacA are transcribed at a high rate.
Tryptophan acts as a corepressor on the lac repressor and turns the lac structural genes on.
Under which conditions is transcription of the lac structural genes high?
Lactose is absent and glucose is scarce.
Lactose is absent and glucose is abundant.
Lactose is present and glucose is scarce.
Lactose is present and glucose is abundant.
Which statement correctly pairs trp control with the usual eukaryotic pattern?
Abundant tryptophan is a corepressor that lets the trp repressor bind the operator and stop transcription of the tryptophan-synthesis genes. Eukaryotes do not typically group metabolic genes into operons; they use transcription factors, enhancers, chromatin packing, and alternative splicing.
The trp operon is inducible and turns on only when tryptophan is abundant. Euchromatin is the tightly packed form that blocks eukaryotic transcription.
The trp repressor is the enzyme that synthesizes tryptophan, and eukaryotes control each metabolic pathway with one shared operator.
Scarce tryptophan makes the trp repressor bind the operator and stop transcription. Eukaryotes keep active genes packed as heterochromatin so those genes are less available.
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