3.8.2 Gene expression and control

Every cell in the body carries the same DNA, but no two cell types express the same genes. 3.8.2 is the layered control system — transcription factors, methylation marks, histone modifications, and post-transcriptional silencing — that decides which genes get read, when, and how strongly.

Stem cells are defined by their potency and their ability to divide before they differentiate.

All cells in a multicellular organism carry the same genome. Differentiation is driven by selective gene expression — switching some genes on and others off without changing the underlying DNA. Stem cells are undifferentiated cells with two defining capacities: self-renewal (they divide to make more stem cells) and differentiation (they give rise to specialised cell types).

Write divide or replicate for stem cell self-renewal, including for iPS cells before they differentiate. AQA rejects differentiate for the self-renewal step (differentiation is what comes next) and rejects grow as a substitute for division.

1. The transplanted stem cells divide or replicate.
2. Healthy blood cells are produced from the dividing stem cell population.
3. No faulty or diseased blood cells are produced — the negative complement is the consistently dropped mark on this chain.

Transcription factors bind specific DNA sequences to switch genes on or off.

Transcription factors are proteins that bind to regulatory DNA sequences adjacent to a gene's coding region. They can activate transcription or repress it. Binding specificity comes from the factor's tertiary structure: a region whose shape is complementary to a specific DNA sequence. The cell's complement of active transcription factors at any moment determines which genes are switched on.

Active site, enzyme, substrate, and induced fit are rejected on transcription factor or hormone receptor questions. The receptor is not an enzyme. Write specific tertiary structure and complementary for the binding language.

1. The transcription factor binds to the promoter region of its target gene.
2. RNA polymerase is stimulated and transcribes the gene into mRNA.
3. The mRNA is translated in the cytoplasm into the gene's protein product.

Oestrogen is the worked example. Oestrogen is a lipid-soluble steroid hormone — mark one. Because it is lipid soluble, it diffuses directly through the phospholipid bilayer of the cell membrane — mark two. The two statements are separately credited; the combined statement lipid soluble so it crosses the membrane earns one mark, not two.

Write lipid soluble and diffuses through the phospholipid bilayer as two separate statements. AQA rejects fat soluble and not water soluble. The two statements have to be separately identifiable for the two-mark separation.

1. Once inside the cytoplasm, oestrogen binds to its receptor protein; the receptor has a specific tertiary structure complementary to oestrogen.
2. Binding changes the receptor's tertiary structure; the DNA-binding region becomes functional.
3. The activated oestrogen-receptor complex enters the nucleus through nuclear pores.
4. The complex binds to the promoter region of its target gene and stimulates transcription.

A mutation that breaks a transcription factor is a mutation in the gene encoding the factor, not in the target gene. The target gene is intact; the factor's tertiary structure is altered, so binding to the target's promoter fails.

siRNA silences genes by destroying their mRNA after transcription.

Small interfering RNA (siRNA) acts after transcription. The target gene is transcribed normally, but the mRNA does not survive long enough to be translated. The siRNA molecule is short, single-stranded, and complementary in sequence to a specific target mRNA.

1. The siRNA binds to its target mRNA by complementary base pairing; a short region of double-stranded RNA forms.
2. The cell detects the double-stranded RNA as abnormal; enzymes degrade the duplex.
3. The targeted mRNA is destroyed; the protein is not translated.

siRNA binds to complementary mRNA, not to DNA and not to the gene. siRNA does not enter the nucleus and does not prevent transcription. Methylation prevents transcription; siRNA blocks translation. The two mechanisms act on different molecules at different stages.

The cross-mechanism distinction matters because it is the topic's most consistent compound error. siRNA targets mRNA in the cytoplasm; methylation targets DNA in the nucleus. Where a question stem names a specific target gene's product, the answer must name the corresponding mRNA — a generic mechanism without naming the target loses the application mark.

Methylation silences genes by blocking transcription; acetylation opens chromatin to allow it.

Epigenetic modifications change gene expression without altering the base sequence. Two mechanisms are examined at AQA: DNA methylation (a methyl group added to cytosine bases) and histone acetylation (an acetyl group added to lysine residues on histone proteins). The two mechanisms work on different molecules and have opposite directional effects.

Write methylation of the promoter region, not methylation of the gene or methylation of the DNA. The promoter is the named binding site, and the credit-bearing detail.

1. Methyl groups attach to cytosine bases in the promoter region of the tumour suppressor gene.
2. Transcription factors cannot bind; the gene is not transcribed; the regulatory protein is not produced.
3. The cell loses its brake on cell division; rapid or uncontrolled cell division follows.

Write deacetylation or tightens histone-DNA binding, not decreased acetylation. AQA wants the active-mechanism phrasing for the gene-off direction.

Pitfall — Methylation drugs work epigenetically, not by mutation

When the question gives a methyltransferase inhibitor or a demethylation drug, the mechanism is epigenetic.

Reduced methylation of a tumour suppressor's promoter lets transcription factors bind again; the gene is now transcribed; the regulatory protein is produced; the brake on cell division is restored.

Writing about a mutation in this context is rejected as a wrong mechanism. The drug does not alter the base sequence; it removes a chemical mark from cytosine bases. Epigenetic, not mutagenic.

Cancer arises when gene expression control fails — most often by silencing a tumour suppressor.

Cancer is uncontrolled cell division producing a tumour. Two gene categories sit at the centre. Proto-oncogenes normally stimulate cell division; mutation or over-expression converts them into oncogenes that drive continuous division. Tumour suppressor genes normally restrain division; silencing removes the brake. The 3.8.2 framing focuses on the gene-expression-control failure routes; mutation-driven changes belong to 3.8.1.

1. Methyl groups attach to cytosine bases in the promoter region of a tumour suppressor gene — BRCA1 in breast cancer is the AQA-credited example.
2. Transcription factors cannot bind; the gene is not transcribed; the regulatory protein is not produced.
3. The cell loses its brake on cell division; rapid or uncontrolled cell division follows, producing a tumour.

Write rapid or uncontrolled cell division, not growth or cell growth. Name tumour suppressor gene specifically, not gene alone. Meiosis is rejected in any cancer answer — tumour cells divide by mitosis.

The oestrogen-cancer link closes the loop. In post-menopausal women, adipose-tissue aromatase produces local oestrogen. The oestrogen activates transcription factors in breast epithelial cells, stimulating transcription of genes that promote cell division. In a cell where BRCA1 has been silenced by hypermethylation, the additional growth-promoting signal tips the cell into uncontrolled division.

Key terms

• transcription factor
• promoter
• transcription
• methylation
• histone
• lipid soluble
• phospholipid bilayer
• complementary
• tumour suppressor
• cell division