IMAT Biology · Molecular Biology and Gene Expression
The Genome, Chromatin and the Control of Genes
Eukaryotic DNA is packed round histones into chromatin, and every cell switches on only the genes it needs: bacteria with operons, eukaryotes at several levels.
Why this matters
The 2024 ministry paper asked what a prokaryotic operon is. Older papers asked what regulates gene expression (2012) and how chromosomes, nucleosomes and histones rank by size (2020).
Concept 1 of 3: Chromatin packing and the organisation of the genome
Each human cell holds about 2 m of DNA in a nucleus a few micrometres wide. It fits because the DNA is wound round protein spools, the histones, and the spools are coiled and looped again and again. The tighter the packing, the harder it is for RNA polymerase to reach a gene.
Definition
The genome is all the DNA of an organism.
- Human nuclear genome: about base pairs per haploid set, on 46 chromosomes in a body cell (22 pairs of autosomes plus XX or XY). The X chromosome is much larger than the Y.
- Only about 1 to 2% of human DNA codes for protein, in roughly 20000 genes; the rest is introns, regulatory sequences, repeated sequences and genes for RNA.
- Histones are small proteins, positively charged, so they bind the negatively charged phosphates of DNA.
- Euchromatin is loosely packed and actively transcribed; heterochromatin is tightly packed and mostly silent.
- Prokaryotes: usually one circular chromosome in the nucleoid, not wrapped round histones, little non-coding DNA, often extra small circles called plasmids. Mitochondria and chloroplasts also have their own circular DNA.
| Level | What it is | Approximate size |
|---|---|---|
| Histone | one small protein; eight (two each of H2A, H2B, H3, H4) form a core | a few nanometres |
| Nucleosome | about 147 base pairs of DNA wound nearly twice round a histone core | about 10 nm across ('beads on a string') |
| Chromatin fibre | nucleosomes packed together, helped by histone H1 | about 30 nm thick |
| Looped domains | the fibre folded in loops on a protein scaffold | a few hundred nanometres |
| Metaphase chromosome | the most condensed form: two sister chromatids | about 1 µm wide and several µm long |
Practice this conceptself-check · 3 quick reps
Rank the packing levels by what contains what
A chromosome contains many nucleosomes, and each nucleosome contains eight histones, so chromosome > nucleosome > histone. Options that put a histone above a nucleosome reverse the nesting.
Concept 2 of 3: The lac operon: switching bacterial genes on with lactose
A bacterium should only make the enzymes for digesting lactose when lactose is there and better food is not. The three lactose genes sit side by side under one switch. A repressor blocks the switch until lactose arrives and pulls the repressor off.
Definition
An operon is a functional unit of prokaryotic DNA: a group of adjacent genes, controlled together and transcribed from one promoter into one mRNA, together with the regulatory sequences.
- The lac operon of E. coli has a promoter, an operator and three structural genes: lacZ (β-galactosidase, which splits lactose into glucose and galactose), lacY (permease, which takes lactose in) and lacA (transacetylase).
- A separate regulatory gene, lacI, with its own promoter, makes the repressor all the time.
- Lactose (as allolactose) binds the repressor and changes its shape, so it leaves the operator: the operon is inducible.
- With glucose present, little cAMP is made, so the activator CAP does not help RNA polymerase and transcription stays low.
- The trp operon is the opposite case, repressible: when tryptophan is plentiful it activates the repressor and the genes switch off.
| Lactose | Glucose | Repressor | Transcription of lacZ, lacY, lacA |
|---|---|---|---|
| absent | present or absent | bound to the operator | off |
| present | present | released (allolactose bound) | low (no help from CAP) |
| present | absent | released (allolactose bound) | high (cAMP and CAP help RNA polymerase bind) |
Practice this conceptself-check · 3 quick reps
The repressor gene is outside the operon and always active
lacI has its own promoter and makes the repressor all the time. Lactose does not stop its production; it binds the repressor and changes its shape so that it falls off the operator.
Concept 3 of 3: Control of gene expression in eukaryotes, in outline
All your body cells carry the same genome, yet a liver cell and a nerve cell make very different proteins. They differ in which genes they use. Eukaryotes have no operons; instead they control each gene at several steps between DNA and finished protein, mostly at transcription.
Definition
Gene expression is the use of a gene's information to make an RNA or protein. In eukaryotes it is controlled at several levels:
- The main point of control is transcription, through transcription factors binding the promoter and distant enhancers (activate) or silencers (repress).
- Differentiation comes from cells expressing different subsets of the same genes; they do not lose the genes they do not use.
- Some hormones act this way: a steroid hormone enters the cell and binds a receptor that works as a transcription factor.
- Housekeeping genes (for example those for glycolysis enzymes) are expressed in almost every cell.
| Level | How expression is controlled |
|---|---|
| Chromatin | acetylating histones loosens chromatin and allows transcription; methylating DNA silences genes |
| Transcription | transcription factors bind promoters, enhancers and silencers to switch genes on or off |
| RNA processing | alternative splicing chooses which exons enter the mRNA |
| mRNA lifetime and translation | microRNAs and the length of the poly-A tail decide how long an mRNA lasts and how often it is read |
| Protein | proteins are activated by modification (for example phosphorylation) or destroyed by the proteasome |
Practice this conceptself-check · 3 quick reps
Transcription factors regulate genes; RNA polymerase only transcribes them
RNA polymerase is needed for every gene and does not choose which genes are used. Gene expression is regulated by transcription factors (and by chromatin, splicing and the other levels), not by replication factors or by organelles such as the rough ER.
Summary — formulas & gotchas at a glance
A revision cheat-sheet for the formulas and gotchas above. Click any concept name to jump back to its full explanation.
Reference tables (3)
Chromatin packing and the organisation of the genome5 rows
| Level | What it is | Approximate size |
|---|---|---|
| Histone | one small protein; eight (two each of H2A, H2B, H3, H4) form a core | a few nanometres |
| Nucleosome | about 147 base pairs of DNA wound nearly twice round a histone core | about 10 nm across ('beads on a string') |
| Chromatin fibre | nucleosomes packed together, helped by histone H1 | about 30 nm thick |
| Looped domains | the fibre folded in loops on a protein scaffold | a few hundred nanometres |
| Metaphase chromosome | the most condensed form: two sister chromatids | about 1 µm wide and several µm long |
The lac operon: switching bacterial genes on with lactose3 rows
| Lactose | Glucose | Repressor | Transcription of lacZ, lacY, lacA |
|---|---|---|---|
| absent | present or absent | bound to the operator | off |
| present | present | released (allolactose bound) | low (no help from CAP) |
| present | absent | released (allolactose bound) | high (cAMP and CAP help RNA polymerase bind) |
Control of gene expression in eukaryotes, in outline5 rows
| Level | How expression is controlled |
|---|---|
| Chromatin | acetylating histones loosens chromatin and allows transcription; methylating DNA silences genes |
| Transcription | transcription factors bind promoters, enhancers and silencers to switch genes on or off |
| RNA processing | alternative splicing chooses which exons enter the mRNA |
| mRNA lifetime and translation | microRNAs and the length of the poly-A tail decide how long an mRNA lasts and how often it is read |
| Protein | proteins are activated by modification (for example phosphorylation) or destroyed by the proteasome |
Watch out for (3)
- Rank the packing levels by what contains what→ Chromatin packing and the organisation of the genome
- The repressor gene is outside the operon and always active→ The lac operon: switching bacterial genes on with lactose
- Transcription factors regulate genes; RNA polymerase only transcribes them→ Control of gene expression in eukaryotes, in outline
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