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Genetics Unit 8: Gene Regulation
Cells control which genes are expressed and when. This unit covers bacterial operons, the logic of cis and trans regulators, and the many layers of eukaryotic regulation.
Covers: Operons and negative control: the lac operon, Positive control: CAP and catabolite repression, Repressible operons and attenuation: trp, Partial diploids and cis/trans analysis, Eukaryotic transcription factors and enhancers, Chromatin, DNA methylation and epigenetics, Post-transcriptional control and miRNAs
Study guide
In bacteria, related genes are often grouped into operons transcribed as one mRNA from a single promoter. The lac operon contains lacZ (β-galactosidase), lacY (permease) and lacA, controlled by an operator next to the promoter. The lacI gene, with its own promoter, makes a repressor that binds the operator and blocks transcription. When lactose is present, some is converted into allolactose, which binds the repressor and releases it from the operator. Because the operon is off until an inducer appears, it is called inducible. This repressor-based switch is negative control.
The lac operon also has positive control. When glucose is scarce, cAMP rises and binds CAP (catabolite activator protein). CAP-cAMP binds near the promoter and helps RNA polymerase start transcription. So the operon is strongly expressed only when lactose is present and glucose is absent. With glucose present, cAMP is low and expression stays low even with lactose; this is catabolite repression, which lets the cell use the preferred sugar first.
Jacob and Monod used partial diploids (merozygotes) to sort regulators into cis and trans. Trans-acting factors are diffusible products, such as the repressor protein, and act on any DNA in the cell: I⁺ is dominant to I⁻, and the super-repressor Iˢ is dominant to I⁺. Cis-acting elements are DNA sites, such as the operator, and control only genes on the same molecule: an Oᶜ operator makes only its adjacent genes constitutive. To solve merozygote problems, ask for each working structural gene whether a repressor can bind its own operator and be released by inducer.
The trp operon is repressible. Its repressor is inactive alone; tryptophan acts as a corepressor that allows it to bind the operator, so high tryptophan shuts the operon off. The trp operon adds attenuation: its leader mRNA can form alternative hairpins. With plenty of tryptophan, a ribosome moves quickly through two trp codons in a leader peptide, and a 3–4 terminator hairpin stops transcription early. When tryptophan is scarce, the ribosome stalls, a 2–3 antiterminator forms instead, and transcription continues. This works because bacterial transcription and translation are coupled.
Eukaryotic regulation has more layers. Chromatin structure controls access: histone acetylation opens chromatin and favors transcription, while DNA methylation at CpG-rich promoters and some histone methylation marks favor silencing. These epigenetic marks can be inherited through cell divisions without changing the DNA sequence. Transcription factors with DNA-binding and activation domains bind promoters and enhancers; enhancers can act far away and in either orientation by DNA looping, and insulators limit their reach. After transcription, alternative splicing, mRNA stability, and microRNAs that pair with target mRNAs fine-tune protein levels.
Key ideas
- The lac operon is inducible and under negative control by the LacI repressor.
- CAP-cAMP provides positive control, so glucose reduces lac expression.
- Trans-acting factors are diffusible products; cis-acting elements are DNA sites that affect only their own molecule.
- Iˢ is dominant and uninducible; Oᶜ is cis-dominant and constitutive.
- The trp operon is repressible and also regulated by attenuation.
- Histone acetylation opens chromatin, and promoter DNA methylation silences genes.
- Enhancers work at a distance through looping; miRNAs silence mRNAs after transcription.
Formulas and rules
Common mistakes
- Calling the operator a gene or a protein; it is a DNA site.
- Forgetting that a normal repressor on an F′ can repress operons on the chromosome.
- Thinking a normal operator elsewhere can rescue an Oᶜ or O⁻ mutation.
- Ignoring CAP-cAMP when glucose is present.
- Confusing histone acetylation (activating) with DNA methylation (silencing).
Before the test, make sure you can
- Predict lac operon expression under any combination of glucose and lactose.
- Explain the roles of LacI, allolactose, the operator, CAP and cAMP.
- Solve partial diploid problems with I⁻, Iˢ, Oᶜ, Z⁻ and Y⁻ mutations.
- Distinguish cis-acting and trans-acting regulators.
- Explain trp repression and attenuation.
- Describe how enhancers, activators and chromatin modifications control eukaryotic genes.
- Explain epigenetic inheritance and miRNA silencing.
Words to know
- Operon
- A group of bacterial genes transcribed together from one promoter and controlled together.
- Operator
- A DNA site bound by a repressor.
- Repressor
- A protein that binds an operator and blocks transcription.
- Inducer
- A molecule that inactivates a repressor, turning genes on (allolactose for lac).
- Corepressor
- A molecule that activates a repressor, turning genes off (tryptophan for trp).
- Inducible operon
- An operon that is normally off and turned on by an inducer.
- Repressible operon
- An operon that is normally on and turned off by a corepressor.
- CAP
- Catabolite activator protein; with cAMP, it stimulates transcription of lac and other operons.
- Catabolite repression
- Reduced expression of operons for other sugars when glucose is present.
- Cis-acting element
- A DNA sequence that affects only genes on the same molecule.
- Trans-acting factor
- A diffusible product, such as a protein, that affects genes on any DNA molecule.
- Partial diploid
- A bacterium carrying a second copy of some genes on an F′ plasmid.
- Attenuation
- Regulation by early termination of transcription in a leader region.
- Enhancer
- A distant DNA element that binds activators to increase transcription.
- Histone acetylation
- Addition of acetyl groups to histones, opening chromatin.
- DNA methylation
- Addition of methyl groups to cytosines, often silencing genes.
- Epigenetics
- Heritable changes in gene expression without changes in DNA sequence.
- MicroRNA
- A short RNA that pairs with target mRNAs to repress them.
Sample practice questions
30 more questions like these, from level 1 to 5, are in the practice set.
In the lac operon, what molecule acts as the inducer by binding the repressor?
- Allolactose
- Tryptophan
- Cyclic AMP bound to its receptor protein
- Glucose
Show the answer and steps
Answer: A) Allolactose
- Lactose is converted in small amounts to allolactose.
- Allolactose binds the LacI repressor and changes its shape so it releases the operator.
- cAMP acts through CAP, a separate positive control, and tryptophan regulates the trp operon.
An operator is best described as:
- A DNA site where a repressor binds to control transcription
- The first structural gene in an operon, transcribed before the others
- A gene that codes for the repressor protein
- A protein that binds DNA and blocks RNA polymerase
Show the answer and steps
Answer: A) A DNA site where a repressor binds to control transcription
- The operator is a DNA sequence, usually overlapping or near the promoter.
- A repressor protein binds it to block transcription.
- The repressor itself is made by a regulatory gene such as lacI.
A partial diploid has genotype I⁻ O⁺ Z⁺ / F′ I⁺ O⁺ Z⁻. How is β-galactosidase expressed?
- Constitutive: with or without lactose
- Never expressed under any condition
- Inducible: only when lactose is present
- Expressed only when lactose is absent from the medium
Show the answer and steps
Answer: C) Inducible: only when lactose is present
- The working Z⁺ is on the chromosome with I⁻.
- The F′ makes normal repressor, which is a diffusible protein and acts on both operators.
- So Z⁺ is repressed until inducer arrives: I⁺ is dominant and acts in trans.