Gene silent but its sequence normal? Suspect regulation: methyl tags, a repressor, or a missing activator.
Your muscle cells and pancreas cells carry the same genome. They differ because they use different genes, and a cell can turn a gene up or down at several steps between DNA and protein.
Key terms
- Differential gene expression — different cells using different parts of the same genome. It's how one genome builds many cell types.
- Regulatory sequence — DNA that codes for no protein but controls when a gene is transcribed. Promoters, enhancers and operators are examples.
- Transcription factor — a protein that binds a regulatory sequence. Activators turn transcription up; repressors turn it down.
- Epigenetic change — a removable chemical tag on DNA or histones. It changes how much a gene is used, not its bases.
- Operon — in bacteria, a set of genes sharing one promoter and one operator, transcribed together into a single mRNA.
- Alternative splicing — keeping different exons from the same pre-mRNA in different cells, so one gene can make several proteins.
How it works
- Packing. DNA methylation at a promoter recruits proteins that pack chromatin tight, silencing the gene. Histone acetylation loosens packing, so the promoter becomes reachable.
- Starting transcription. Transcription factors bind regulatory sequences. Activators help RNA polymerase start at the promoter; repressors prevent it. This is the most common control point.
- In bacteria, a repressor on the operator blocks RNA polymerase from the whole operon. A signal molecule changes the repressor's shape, switching every gene on or off together.
- Processing. Alternative splicing keeps different exons in different cell types, so one gene yields different proteins. Regulatory proteins in each cell decide which exons stay.
- Last, the protein. An end product can shut off an enzyme that already exists — feedback inhibition. It acts in seconds; shutting down the gene takes minutes.
Why it matters
Expect data: enzyme levels with and without a signal, or mRNA levels across tissues. Your move is to compare the conditions, find where the switch differs or failed, and name the level: packing, transcription, splicing, or the protein. This topic also sets up the next one, where transcription factors turn one genome into many specialized cells.
Exam traps
| Trap | Actually |
|---|
| Specialized cells delete the genes they don't use. | They keep the whole genome. Cell types differ in which genes they transcribe, not in which genes they carry. |
| A strain making lots of enzyme with no inducer has a better enzyme. | Read the no-inducer column first. High output there means the off switch failed: the repressor no longer holds the operator. |
| A factor found wherever a gene is active must be switching it on. | That's an association. Showing cause takes an experiment: add or remove the factor, then watch the gene respond. |
| Two tissues making different proteins from one gene must carry different versions of it. | Same gene, same pre-mRNA. Alternative splicing keeps different exons in each tissue, so the proteins differ. |
Worked example
Tumor cells make no mRNA from gene T, which normally limits cell division. Sequencing shows gene T and its promoter have a normal base sequence, but the promoter's cytosines are heavily methylated. After several divisions with a drug that blocks DNA methylation, the cells make gene T mRNA again. What best explains gene T's silence?
- The sequence is normal, so a mutation in gene T or its promoter is ruled out.
- Heavy methylation at a promoter recruits proteins that pack chromatin tight, so transcription factors and RNA polymerase can't reach it.
- The drug stops the tags from being copied onto new DNA. Division by division, the promoter loses its methylation, opens up, and transcription returns.
Epigenetic silencing. Methyl tags on the promoter packed gene T away, so the gene was intact but unreadable.
Two clues point the same way: the sequence is unchanged, and the silence reverses when methylation is blocked. A mutation would not undo itself when a drug arrived. The near miss is 'a promoter mutation blocks RNA polymerase' — right location, wrong cause, because the bases there are normal.