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Unit 6 · Topic 6.5

6.5 Regulation of Gene Expression

Cells don't use all their genes all the time. Regulatory DNA sequences and the proteins that bind them decide which genes are transcribed and how much, bacteria group related genes into operons that switch on or off together, and epigenetic marks on DNA and histones change expression without changing the sequence.

Key terms

  • regulatory sequence
  • operon
  • inducible
  • repressible
  • epigenetics
  • transcription factor

Why regulate genes?

Making RNA and protein costs energy and materials. A bacterium that made every enzyme all the time would waste resources, and a multicellular organism needs different cells to make different products. A cell's phenotype depends on which genes are expressed and at what levels, so regulation is how one genome produces many outcomes.

Some genes are constitutive, meaning they're expressed all the time at a steady level, because their products are always needed (for example, genes for glycolysis enzymes or ribosome parts). Others are inducible: normally off, switched on when a signal or substance appears.

Regulatory sequences and proteins

Regulatory sequences are noncoding pieces of DNA that control whether a nearby gene is transcribed. Regulatory proteins bind to them. Repressors block transcription, and activators help RNA polymerase start. Where a regulatory sequence sits relative to the gene matters, because the protein bound there has to interfere with or help RNA polymerase at the promoter.

Operons in bacteria

In prokaryotes, genes for related functions are often grouped into an operon: one promoter, an operator (a regulatory sequence where a repressor can bind, overlapping or next to the promoter), and several genes transcribed together into one mRNA. One switch controls them all.

Featurelac operon (inducible)trp operon (repressible)
What the genes doBreak down the sugar lactoseMake the amino acid tryptophan
Default stateOffOn
Repressor aloneActive: binds the operator and blocks transcriptionInactive: can't bind the operator
Signal moleculeA form of lactose (allolactose) binds the repressor and inactivates itTryptophan binds the repressor and activates it
ResultLactose present → genes onTryptophan plentiful → genes off
Makes sense becauseOnly make lactose enzymes when there's lactose to useStop making tryptophan when there's already enough

Positive control and coordinated genes

The lac operon also has positive control. When glucose, the cell's preferred sugar, is scarce, an activator protein (CAP, bound to a signal molecule called cAMP) binds near the promoter and helps RNA polymerase attach. So the lac genes are expressed strongly only when lactose is present and glucose is low.

Eukaryotes generally don't have operons, but they still coordinate genes: several genes scattered across different chromosomes can share the same regulatory sequence, so one transcription factor switches them all on together, such as all the genes needed in a stress response.

Epigenetics and development

Epigenetic changes alter gene expression without changing the DNA sequence, and they're reversible. Adding methyl groups to DNA (DNA methylation) usually silences genes. Chemical tags on histones change how tightly DNA is packed: acetylation loosens chromatin so genes are easier to transcribe, while removing acetyl groups packs it tighter and lowers expression. These marks can be copied when cells divide, so a liver cell's daughter cells stay liver cells.

During development, transcription factors switch on in a sequence: one factor turns on genes for the next factors, which turn on the next set. This cascade gradually commits cells to particular fates. Cell differentiation is visible because each specialized cell makes its own tissue-specific proteins, like hemoglobin in red blood cell precursors or keratin in skin cells.

Worked examples

Try each one yourself first, then open the solution.

  1. Example 1

    Predicting lac operon mutants

    Predict whether the lac genes are transcribed (lactose present, glucose absent) in each E. coli strain: (a) normal cells; (b) the operator is mutated so the repressor can't bind; (c) the repressor is mutated so it can't bind allolactose but can still bind the operator. Then predict each strain with no lactose.

    Show the solution
    1. Step 1: (a) Normal cells: with lactose, allolactose binds the repressor, it releases the operator, and the genes are transcribed. Without lactose, the repressor sits on the operator: off.
    2. Step 2: (b) Operator mutant: the repressor can never bind, so nothing blocks RNA polymerase. The genes are on with or without lactose (constitutive expression).
    3. Step 3: (c) Repressor mutant: the repressor binds the operator but can't be removed by allolactose. The genes stay off with or without lactose.
    4. Step 4: Reasoning pattern: ask whether the repressor can sit on the operator in each condition.

    Answer: (a) On with lactose, off without. (b) On in both conditions. (c) Off in both conditions.

  2. Example 2

    Reasoning about a repressible operon

    Bacteria growing in a medium with no tryptophan are moved to a medium rich in tryptophan. Predict what happens to the amount of trp operon mRNA, and explain.

    Show the solution
    1. Step 1: Without tryptophan, the trp repressor is inactive, so the trp genes are transcribed and the cell makes its own tryptophan.
    2. Step 2: In the new medium, tryptophan enters the cell and binds the repressor, activating it.
    3. Step 3: The active repressor binds the operator and blocks RNA polymerase.
    4. Step 4: Transcription stops, and existing trp mRNA breaks down, so the amount falls. The cell saves energy by using the tryptophan from the medium instead of making it.

    Answer: trp operon mRNA decreases, because tryptophan activates the repressor, which binds the operator and shuts off transcription.

Common mistakes

  • Saying lactose activates the lac repressor. Allolactose inactivates it; in the trp operon, tryptophan is what activates the repressor.
  • Calling epigenetic changes mutations. They change expression, not the base sequence, and they can be reversed.
  • Saying histone acetylation silences genes. Acetylation loosens chromatin and generally increases transcription; DNA methylation usually silences genes.
  • Forgetting that operons are mainly a prokaryote feature; eukaryotes coordinate genes through shared regulatory sequences and transcription factors.

On the exam

  • Operon questions often describe a mutation in the operator, promoter or repressor and ask you to predict expression with and without the signal molecule. Walk through whether the repressor can bind.
  • When explaining how cells with the same DNA differ, use regulation language: different transcription factors, different regulatory sequences being used, or epigenetic marks.

Connected topics

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Check yourself

4 questions on 6.5 Regulation of Gene Expression. Pick an answer to see if you got it, and why.

Question 1 of 4

The trp operon in E. coli contains genes for making the amino acid tryptophan. When tryptophan is abundant in the cell, it binds the operon's repressor. Which outcome best describes this regulation?

Question 2 of 4

Identical twins have the same DNA sequence, but as they age, their patterns of DNA methylation become more different, and so do some of their traits. Which statement best explains this?

Question 3 of 4

In E. coli, the trp operon's genes make enzymes that build the amino acid tryptophan. A mutant has a repressor protein that cannot bind tryptophan. What is the most likely effect when tryptophan levels in the cell are high?

Question 4 of 4

Adding acetyl groups to histones loosens how tightly DNA is wrapped around them. A drug blocks the enzymes that remove these acetyl groups. Which effect on many genes is most likely?

0 of 4 answered