Regulation of transcription and translation (A-level only)
AQA
A-Level
A transcriptional factor is a protein that controls whether a particular gene is transcribed. Many are held inactive in the cytoplasm until a signal arrives; once activated they pass through a nuclear pore into the nucleus and bind to a specific base sequence in the promoter region, the stretch of DNA lying just before the gene. The binding site of the factor is complementary in shape to that sequence, so each factor only affects its own target genes. A stimulatory factor helps RNA polymerase attach to the promoter, so transcription begins, mRNA is produced and the polypeptide is made. An inhibitory factor blocks the promoter, so RNA polymerase cannot bind and no mRNA is transcribed. The gene itself is unchanged in every case; only the amount of mRNA changes.
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Objectives
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Exam Tips
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Pitfalls
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Key Terms
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Mark Points
Subtopics in this area
In eukaryotes, transcription of target genes can be stimulated or inhibited when specific transcriptional factors move from the cytoplasm into the nucleus.
The role of the steroid hormone, oestrogen, in initiating transcription.
Epigenetic control of gene expression in eukaryotes.
Epigenetics involves heritable changes in gene function, without changes to the base sequence of DNA. These changes are caused by changes in the environment that inhibit transcription by: increased methylation of the DNA or decreased acetylation of associated histones.
The relevance of epigenetics on the development and treatment of disease, especially cancer.
In eukaryotes and some prokaryotes, translation of the mRNA produced from target genes can be inhibited by RNA interference (RNAi).
Students should be able to: interpret data provided from investigations into gene expression evaluate appropriate data for the relative influences of genetic and environmental factors on phenotype.
Regulation of transcription and translation (A-level only) Revision Guide
Learning Objectives
What you need to know and understand
- Describe the route an activated transcriptional factor takes from the cytoplasm to the promoter region, naming the nuclear pore and the base sequence it binds.
- Explain how the presence or absence of a transcriptional factor at the promoter changes the quantity of mRNA and therefore of polypeptide made.
- Suggest why a bacterium given a human gene may produce no protein, referring to the transcriptional factors it lacks.
- Describe how a lipid-soluble hormone reaches its receptor inside a cell and what the change in tertiary structure does to the receptor.
- Explain, step by step, how an oestrogen-receptor complex increases transcription of a target gene in the nucleus.
- Suggest how a drug shaped like oestrogen reduces transcription in an ER-positive tumour, linking receptor binding to the amount of mRNA produced.
- Explain how the charge on a histone changes when acetyl groups are added or removed, and what this does to the accessibility of the DNA.
- Describe where methyl groups are added and why their presence stops transcription factors binding.
- Distinguish an epigenetic change from a mutation by stating precisely what is and is not altered in the DNA.
- State the definition of epigenetics in a form that makes clear the base sequence is unaltered.
- Explain why increasing methylation of a promoter and decreasing acetylation of histones both have the same effect on transcription.
- Describe how an environmental factor can change the expression of a gene in an individual and in that individual's daughter cells.
- Explain how hypermethylation of a tumour suppressor gene leads to uncontrolled cell division without any mutation occurring.
- Suggest, in the correct direction, how a drug altering methylation or acetylation could treat a tumour.
- Justify why epigenetic changes can be promising drug targets, referring to what is and is not altered in the DNA.
- Describe how siRNA is produced from double-stranded RNA and what it combines with in the cytoplasm.
- Explain why an mRNA molecule targeted by siRNA yields no polypeptide, naming the stage of protein synthesis that is blocked.
- Distinguish RNA interference from control by transcriptional factors by stating where in the pathway each one acts.
- Describe a trend in gene expression data by quoting figures with units and comparing the relevant groups.
- Decide, from error bars or standard deviations, whether a difference in expression is significant, and say why.
- Explain how a study using monozygotic twins separates the contribution of alleles from that of the environment and other factors.
Marking Points
Key points examiners look for in your answers
- one mark for the transcriptional factor moving from the cytoplasm into the nucleus, through a nuclear pore
- one mark for it binding to a specific base sequence in the promoter region of the target gene
- one mark for RNA polymerase being stimulated or activated, so transcription of the gene occurs
- one mark for the converse, that if the factor does not bind then fewer transcriptional factors are at the promoter and less or no mRNA is transcribed
- one mark, in a genetic engineering context, for bacteria not having the required transcriptional factors and so being unable to transcribe the gene
- one mark for oestrogen being lipid-soluble and diffusing through the cell-surface membrane
- one mark for oestrogen binding to a specific receptor on the transcriptional factor and changing its tertiary shape, activating it
- one mark for the oestrogen-receptor complex entering the nucleus and binding to the promoter region
- one mark for RNA polymerase being stimulated or activated, so the target gene is transcribed
- one mark, for a drug question, for the drug binding the oestrogen receptor and preventing oestrogen binding, so no or fewer transcriptional factors bind the promoter
- Increased methylation of DNA or the promoter region inhibits transcription.
- Decreased acetylation of associated histones inhibits transcription, while increased acetylation stimulates it.
- Less acetylation makes histones bind DNA more tightly, condensing DNA so transcription factors or RNA polymerase cannot bind.
- The base sequence of the DNA remains unchanged during epigenetic modification.
- Environmental factors can alter epigenetic tags, and these changes can be passed on to daughter cells during replication.
- one mark for defining epigenetics as a heritable change in gene function with no change to the base sequence of the DNA
- one mark for increased methylation of the DNA or gene, accepting the promoter region, inhibiting transcription or expression
- one mark for decreased acetylation of histones inhibiting transcription or expression
- one mark for the converse pair, decreased methylation or increased acetylation stimulating transcription
- one mark for identifying a change in the environment as the cause of the altered methylation or acetylation
- Increased methylation of a tumour suppressor gene promoter, so the gene is not transcribed and the protein that slows the cell cycle or triggers apoptosis is not made.
- Decreased methylation or increased acetylation of histones associated with an oncogene, so it is transcribed more and cell division is stimulated.
- Linking the methylation or acetylation change to inhibiting or stimulating transcription or expression of the gene.
- Explaining that the change is reversible because the base sequence of the DNA is not altered.
- Naming a drug class and its effect, such as a DNA methyltransferase inhibitor reducing methylation so a tumour suppressor gene is expressed again, or a histone deacetylase inhibitor increasing acetylation.
- one mark for double-stranded RNA being cut by an enzyme into small sections of siRNA
- one mark for one strand of the siRNA combining with an enzyme or protein complex in the cytoplasm
- one mark for the siRNA bases pairing with complementary bases on the target mRNA
- one mark for the mRNA being cut or hydrolysed, so it cannot be translated at a ribosome
- one mark for concluding that the polypeptide is not produced, so the gene is not expressed
- Describe the pattern using figures quoted from the graph or table, including units.
- Use error bars, standard deviations or statistical tests to state whether a difference is significant.
- Identify controlled variables that allow conclusions, such as identical genotypes highlighting environmental or epigenetic differences.
- Explain the result using a named mechanism of gene expression, such as transcription factors, methylation, acetylation or RNAi.
- State a valid limitation, such as correlation not showing causation, small sample sizes, or short study durations.
Examiner Tips
Expert advice for maximising your marks
- 💡Write 'promoter region' every time; 'binds to the DNA' is too vague to gain the binding mark.
- 💡Make the direction explicit - say whether transcription is stimulated or inhibited, and finish with what happens to the amount of mRNA.
- 💡Keep enzyme language out of it: a transcriptional factor has a binding site, not an active site.
- 💡Build the chain in order: lipid-soluble, diffuses in, binds receptor, shape change, into nucleus, promoter, RNA polymerase, transcription.
- 💡In ER-positive breast cancer questions each of the three marks is a separate link - receptor binding, oestrogen blocked, fewer factors at the promoter.
- 💡Name the receptor as a transcriptional factor if you can; mark schemes accept 'inactive transcriptional factor' for receptor.
- 💡Learn the pairing: methylation of DNA, acetylation of histones. Mixing them up loses marks.
- 💡Always convert 'switched on or off' into 'transcription is stimulated or inhibited'.
- 💡The specification wording is a reliable guide to what is expected: increased methylation of DNA, decreased acetylation of histones. Use that phrasing.
- 💡State the direction before the effect - 'increased methylation of the DNA inhibits transcription' scores, 'methylation affects transcription' does not.
- 💡For a definition mark, include the idea that the base sequence of DNA is unchanged.
- 💡Keep two columns in your head: a tumour suppressor gene needs re-expressing, an oncogene needs silencing, and work out the methylation direction from that.
- 💡Read whether the question asks for the cause of a tumour or a possible treatment - the same facts are marked differently.
- 💡Reversibility is the usual 'why is this a promising treatment' mark; say the base sequence is unchanged.
- 💡Anchor the answer with the word 'complementary' next to the word 'mRNA' - that pairing is where the mark sits.
- 💡Finish every RNAi answer with 'so the polypeptide is not produced', which is usually the last mark.
- 💡Say explicitly that this happens after transcription, to show you know the level of control being described.
- 💡Split your answer: first describe the data with figures, then provide the biological explanation.
- 💡When error bars or standard deviations are shown, state whether they overlap and what this means for significance before concluding.
Common Mistakes
Pitfalls to avoid in your exam answers
- writing that the transcriptional factor 'binds to the gene' without ever naming the promoter region
- describing the factor binding DNA as an active site and an enzyme-substrate complex, which examiners reject in this topic
- saying the transcriptional factor makes the protein, instead of controlling transcription of mRNA
- claiming the factor alters the base sequence of the gene, which would be a mutation, not regulation
- assuming prokaryotes regulate transcription with the same transcriptional factors as eukaryotes
- describing oestrogen binding its receptor as forming an enzyme-substrate complex or entering an active site, which is explicitly rejected
- saying oestrogen binds to a receptor on the outside of the cell-surface membrane, as a protein hormone would
- saying oestrogen itself binds to the promoter, when it is the activated receptor complex that does
- writing that the oestrogen-like drug 'kills the cancer cells' with no mention of receptors or transcription
- leaving out the shape change, so there is nothing to explain why the factor becomes active
- Swapping the pairs and writing 'methylation of histones' or 'acetylation of DNA', which is incorrect. Correction: learn the specific pairings of DNA methylation and histone acetylation.
- Stating 'the gene is switched off' without linking it to the inhibition of transcription or gene expression. Correction: always use precise terms like 'transcription is inhibited'.
- Calling an epigenetic change a mutation; mutations alter the base sequence, whereas epigenetics does not. Correction: explicitly state that the DNA base sequence is unchanged.
- Claiming that epigenetic changes cannot be inherited. Correction: epigenetic tags can be maintained during DNA replication and passed to daughter cells.
- writing 'methylation of histones' or 'acetylation of DNA' - examiners ignore both, so the whole mark is lost
- saying the gene is 'switched off' with no reference to transcription or expression, which is ignored
- claiming epigenetic changes alter the DNA base sequence, which contradicts the definition being tested
- getting the direction wrong and writing that increased acetylation inhibits transcription
- saying the change cannot be inherited, when heritability is part of the definition
- Offering epigenetic modification as the explanation when the question is about a mutation causing a tumour - examiners ignore epigenetics in that context and want a change in base sequence. Correction: state that a mutation changes the base sequence, whereas epigenetic changes do not.
- Reversing the treatment logic and methylating the tumour suppressor gene rather than reducing its methylation. Correction: a tumour suppressor gene needs to be re-expressed, so its methylation should be reduced.
- Writing 'acetylation of DNA' or 'methylation of histones' in a treatment answer. Correction: acetylation occurs on histones, methylation can occur on DNA or histones.
- Saying an epigenetic drug 'cures cancer' without naming the enzyme inhibited or the effect on transcription. Correction: name the enzyme and state the effect on transcription.
- Confusing an epigenetic silencing of a tumour suppressor gene with the gene being deleted. Correction: the gene is still present but not transcribed.
- saying RNAi stops transcription, when the mRNA has already been transcribed and the block is at translation
- saying the siRNA binds to the DNA or to the gene rather than to the mRNA
- describing siRNA as complementary to the template strand of the gene instead of to the mRNA
- confusing siRNA with tRNA, so writing about anticodons and amino acids
- saying the protein is broken down, when it is the mRNA that is destroyed and the protein is never made
- Writing 'the results are significant' without specifying what is greater, lower or different.
- Describing the graph in detail but failing to explain it biologically using gene expression mechanisms.
- Assuming phenotypic differences in monozygotic twins are exclusively environmental, ignoring somatic mutations or epigenetic factors.
- Treating a correlation between an environmental factor and expression as proof of causation.