AP® Biology review sheet from Aim for Five (aimforfive.com/bio/units/6/6-6)
Unit 6 · Topic 6.6
6.6 Gene Expression and Cell Specialization
Almost every cell in your body carries the same genome, so cells become different by expressing different genes. Transcription factors binding promoters and enhancers switch genes on, repressor proteins switch them off, and small RNA molecules can block a gene's mRNA after it's made.
Key terms
- differential gene expression
- promoter
- enhancer
- transcription factor
- repressor
- small regulatory RNA
Same DNA, different cells
A neuron, a muscle cell and a skin cell in your body have essentially the same DNA. They look and act different because of differential gene expression: each cell type transcribes its own set of genes. A muscle cell makes lots of the contractile proteins actin and myosin; a pancreatic cell makes insulin; a red blood cell precursor makes hemoglobin. Gene regulation decides which products a cell makes and how much, and those products determine the cell's structure and function.
Promoters, enhancers and transcription factors
In eukaryotes, RNA polymerase can't start transcription on its own. It needs transcription factors, proteins that bind to specific DNA sequences. Some bind at the promoter, the sequence where transcription begins. Others bind to enhancers, regulatory sequences that can sit far from the gene, either upstream (before the start site) or downstream (after it). DNA can loop around so that proteins bound at a distant enhancer contact the proteins at the promoter and help RNA polymerase get going.
Each gene has its own combination of regulatory sequences, and each cell type has its own mix of transcription factors. A gene is transcribed strongly only when the right combination of factors is present. That's how a small number of factors, used in different combinations, can control thousands of genes in different patterns.
Turning genes off
Negative regulatory molecules, often called repressors, bind DNA and block transcription, for example by covering a binding site that an activator or RNA polymerase needs. Expression of a gene reflects the balance between the activators and repressors bound near it.
Small regulatory RNAs
Gene expression can also be controlled after transcription. Small RNA molecules, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), are only about 20 to 25 nucleotides long. They join with proteins and base-pair with complementary sequences in a target mRNA. Then the target mRNA is either broken down or blocked from being translated. Either way, less protein is made even though the gene is still being transcribed.
This adds another layer of control. Scientists also use the same idea in the lab, designing small RNAs to silence a specific gene so they can see what that gene does.
Levels of control
Putting 6.3 through 6.6 together, a cell can adjust how much of a protein it makes at several points:
- Chromatin packing and epigenetic marks: whether DNA is accessible at all.
- Transcription: which transcription factors and repressors are bound at promoters and enhancers.
- RNA processing: which exons are kept through alternative splicing.
- After transcription: how long the mRNA lasts and whether small RNAs block it.
- Translation and beyond: how often the mRNA is translated and how long the protein lasts.
Worked examples
Try each one yourself first, then open the solution.
- Example 1
Predicting an enhancer mutation
Gene X is expressed in liver cells but not skin cells. Gene X has an enhancer 2,000 base pairs upstream of its promoter. A mutation changes the enhancer so a liver-specific transcription factor can no longer bind. Predict the effect on gene X in liver cells and in skin cells, and explain.
Show the solutionHide the solution
- Step 1: In liver cells, the liver-specific factor normally binds the enhancer; the DNA loops so the factor helps RNA polymerase start at the promoter.
- Step 2: With the mutation, the factor can't bind, so transcription of gene X in liver cells drops (to a low level or none).
- Step 3: Skin cells don't make the liver-specific factor, so gene X was already off there; the mutation causes no change.
- Step 4: Notice the gene's coding sequence is unchanged; the protein made would be normal, just in smaller amounts.
Answer: Gene X expression falls sharply in liver cells and stays off in skin cells, because the enhancer can no longer recruit the liver-specific transcription factor.
- Example 2
Interpreting small-RNA data
Researchers add a small RNA complementary to the mRNA of gene Y to cultured cells. Gene Y mRNA made per hour by transcription stays the same, but the amount of gene Y protein falls by 80%. Explain these results.
Show the solutionHide the solution
- Step 1: Transcription is unchanged, so the small RNA didn't affect the promoter, enhancers or transcription factors.
- Step 2: The small RNA base-pairs with gene Y mRNA after it is made.
- Step 3: Once bound (with its partner proteins), it causes the mRNA to be broken down or blocks the ribosome from translating it.
- Step 4: So less protein is made from the same amount of transcription.
Answer: The small RNA silences gene Y after transcription by pairing with its mRNA and causing it to be degraded or not translated, so protein levels drop while the transcription rate is unchanged.
Common mistakes
- Saying different cell types have different DNA. They have the same genome but express different genes.
- Thinking enhancers must sit right next to the gene. They can be far upstream or downstream and still work, because DNA loops.
- Saying small regulatory RNAs change the DNA or stop transcription. They act on mRNA after transcription.
- Confusing promoters and enhancers. The promoter is where transcription starts; enhancers are additional binding sites that boost transcription.
On the exam
- Claim-evidence-reasoning questions are common here: make a claim about how a regulatory change affects a cell's phenotype, support it with the data, and explain the mechanism (factor binding, repressor binding or mRNA silencing).
- Watch whether data show changes in mRNA levels or protein levels; that tells you whether the control acts at transcription or after it.
Connected topics
Videos
Check yourself
5 questions on 6.6 Gene Expression and Cell Specialization. Pick an answer to see if you got it, and why.
A liver cell and a nerve cell from the same person contain the same genes but make very different sets of proteins. Which of the following best explains this?
A gene is expressed strongly in muscle cells but not in skin cells. Researchers find a DNA sequence 10,000 base pairs upstream of the gene. When this sequence is deleted, expression in muscle cells drops sharply but the gene's coding sequence is unchanged. This sequence most likely is
A cell begins making a short RNA molecule that is complementary to part of a particular mRNA. Researchers find that the mRNA is still made but the protein it codes for drops sharply. Which explanation is best supported?
| DNA construct | Expression in liver cells (%) | Expression in kidney cells (%) |
|---|---|---|
| Promoter + region E1 + region E2 | 100 | 100 |
| Promoter + region E2 (E1 deleted) | 9 | 96 |
| Promoter + region E1 (E2 deleted) | 97 | 11 |
| Regions E1 + E2 (promoter deleted) | 0 | 0 |
Experimental data: a gene that is normally active in both liver and kidney cells was attached to a reporter gene whose product is easy to measure. Different regulatory regions were deleted, and each construct was put into liver cells and kidney cells. Expression is shown as a percent of the full construct in the same cell type.
Which claim is best supported by the data?
What does the result for the construct without a promoter best show?
0 of 5 answered