Topic 6.5 Notes – Regulation of Gene Expression

1. Gene Expression and Why It Determines Phenotype

Every somatic cell in your body has essentially the same DNA. What makes a neuron different from a muscle cell is which genes are expressed and how much they are expressed.

Gene expression = transcription + translation → gene product (usually protein).
Only expressed genes affect phenotype.

Phenotype depends on:

• Which genes are turned on
• How much protein is made
• The function of that protein

A small change in expression level can change a trait. On exams, they love giving data showing increased mRNA levels and asking you to predict the phenotypic effect. Always think: more mRNA → usually more protein → stronger effect of that protein’s function.

Constitutive vs Regulated Genes

Not all genes are controlled the same way.

• Constitutive genes
  • Always on
  • Encode proteins needed for basic cell function
  • Often called “housekeeping genes” (e.g., enzymes for glycolysis)
• Regulated genes
  • Turned on or off depending on conditions
  • May be inducible (turned on by a signal) or repressible (turned off by a signal)

Gene Expression and Cell Differentiation

Differentiation happens because different cell types express different sets of genes.

Examples of tissue-specific proteins:

• Muscle cells → actin and myosin (contraction)
• Neurons → ion channels and neurotransmitter receptors
• Pancreatic beta cells → insulin

Observable differences come from selective gene expression, not different DNA. That distinction shows up constantly in multiple choice questions.

Sequential Gene Expression in Development

Development follows a gene activation cascade.

1. Early transcription factors are expressed.
2. Those activate other transcription factors.
3. Downstream genes are turned on in sequence.
4. Cells progressively specialize.

The order matters. If an early transcription factor is mutated, every downstream gene in that pathway can be affected. When the AP gives you a mutation in a “master regulator,” expect widespread developmental effects.

Big idea: Phenotype = combination of genes expressed + level of expression.

2. Regulatory Sequences and Transcription Factors

Most regulation happens at transcription. DNA has specific noncoding regions that control whether RNA polymerase can transcribe a gene.

Regulatory DNA Sequences

These are binding sites for regulatory proteins.

Promoters

• Located directly upstream of a gene
• RNA polymerase binding site
• Required to start transcription

If a promoter is mutated, transcription usually drops or stops entirely.

Enhancers

• Increase transcription rate
• Can be far from the gene (upstream, downstream, or within introns)
• Work through DNA looping
• Bind activator transcription factors

In the diagram below, an activator protein is bound to a distant enhancer. DNA bends so that this activator can interact with RNA polymerase at the promoter of the gene.

Enhancer-promoter interaction through DNA looping

Distance does not matter as long as DNA looping brings enhancer-bound proteins to the promoter.

Silencers

• Decrease transcription
• Bind repressor proteins

Operators (prokaryotes)

• Located within operons
• Repressor binding site
• Positioned to physically block RNA polymerase

Location connects to function.
Promoters sit right next to genes because they are the start site. Enhancers can be far away because looping solves the distance problem. Operators sit where they can physically block transcription.

Mutations in regulatory sequences can:

• Increase expression (e.g., stronger enhancer)
• Decrease expression
• Eliminate expression entirely

These mutations often change phenotype without changing the protein’s amino acid sequence.

3. Epigenetic Regulation of Gene Expression

Epigenetics changes gene expression without changing the DNA sequence.

It works by changing how tightly DNA is packaged.

DNA Methylation

• Adds -CH₃ groups to cytosine
• Usually silences genes
• Blocks transcription factor binding
• Often long-term but reversible
• Can be inherited through cell division

Histone Modifications

DNA wraps around histones to form chromatin. The degree of packing determines whether genes are accessible for transcription.

Euchromatin and heterochromatin in an interphase nucleus

• Acetylation → loosens chromatin → increases transcription
• Deacetylation → tightens chromatin → decreases transcription
• Histone methylation can activate or repress depending on location

Key pattern to memorize:

• Loose chromatin (euchromatin) → high transcription
• Tight chromatin (heterochromatin) → low transcription

Environmental factors can influence epigenetic marks. On FRQs, they often describe an environmental exposure and ask you to explain changes in gene expression without DNA mutation.

4. Coordinated Gene Regulation in Prokaryotes and Eukaryotes

Cells often regulate groups of genes together.

Prokaryotes Use Operons

An operon is a cluster of genes transcribed as one mRNA.

Components:

• Promoter
• Operator
• Structural genes
• Regulatory gene (makes repressor)

All genes turn on or off together.

Inducible vs Repressible Operons

Pattern to remember:
Cells avoid wasting energy. If the product is already present, shut down synthesis.

Eukaryotes Use Shared Transcription Factors

Eukaryotes do not use operons.

Instead:

• Genes in the same pathway share common enhancer sequences
• The same transcription factor can activate multiple genes across the genome
• Coordination happens through shared regulatory proteins, not physical clustering

Examples include hormone-responsive genes, heat shock genes, and cell cycle genes.

Prokaryotes cluster genes physically.
Eukaryotes coordinate genes functionally through shared control elements.