Regulation of Gene Expression Notes - Campbell Biology 10th Edition

Differential Expression of Genes

• Environmental Response: Both prokaryotes and eukaryotes precisely regulate gene expression in response to environmental conditions.
• Multicellular Development: In multicellular eukaryotes, gene expression regulates development and is responsible for the differences in cell types despite identical genomes.
• Regulatory RNA: RNA molecules play many roles in regulating gene expression in eukaryotes.

Concept 18.1: Bacterial Regulation of Transcription

• Natural Selection: Evolution has favored bacteria that produce only the specific products needed by that cell at a given time.
• Metabolic Control: A cell can regulate the production of enzymes through two primary routes:
  • Feedback Inhibition: Regulating the activity of enzymes already present (e.g., the end product of a pathway inhibits the first enzyme in the pathway).
  • Gene Regulation: Regulating the production of enzymes by controlling the transcription of the genes that encode them.
• The Operon Model: This is a key mechanism for the control of gene expression in bacteria.

The Basic Concept of Operons

• Coordinate Control: A cluster of functionally related genes can be controlled by a single "on-off switch."
• Operator: The "switch" is a segment of DNA called an operator, which is usually positioned within the promoter or between the promoter and the enzyme-coding genes.
• Operon Definition: The entire stretch of DNA that includes the operator, the promoter, and the genes they control.
• Repressor Protein: The operon can be switched off by a protein repressor.
  • The repressor prevents gene transcription by binding to the operator and physically blocking RNA polymerase.
  • Regulatory Gene: The repressor is the product of a separate regulatory gene, located some distance from the operon it controls.
• Corepressors: A corepressor is a molecule that cooperates with a repressor protein to switch an operon off.
  • Repressors can exist in active or inactive forms, depending on the presence of these corepressor molecules.

The Trp Operon: A Repressible Operon

• Synthesis of Tryptophan: E. coli can synthesize the amino acid tryptophan when it has insufficient levels of it.
• Default State: By default, the trp operon is "on," and the genes for tryptophan synthesis are transcribed.
• Mechanism of Inactivation:
  • When tryptophan is present, it acts as a corepressor and binds to the trp repressor protein.
  • Binding activates the repressor, allowing it to bind to the operator and turn the operon off.
  • The trp operon is turned off (repressed) only if tryptophan levels are high.
• Structural Components of the trp Operon:
  • Regulatory Gene: $trpR$.
  • Genes of Operon: $trpE$, $trpD$, $trpC$, $trpB$, and $trpA$.

Repressible vs. Inducible Operons: Negative Gene Regulation

• Negative Control: Both repressible and inducible operons are types of negative gene regulation because the active form of the repressor protein switches off the operon.
• Repressible Operon:
  • Usually "on."
  • Binding of a repressor to the operator shuts off transcription.
  • Example: The trp operon.
  • Typically functions in anabolic (biosynthetic) pathways; synthesis is repressed by high levels of the end product.
• Inducible Operon:
  • Usually "off."
  • A molecule called an inducer inactivates the repressor and turns on transcription.
  • Example: The lac operon.
  • Typically functions in catabolic (degradative) pathways; synthesis is induced by a chemical signal.

The Lac Operon: An Inducible Operon

• Function: Contains genes coding for enzymes used in the hydrolysis and metabolism of lactose.
• Repressor State: By itself, the lac repressor is active and keeps the lac operon "off."
• Inducer Mechanism:
  • Allolactose: An isomer of lactose that acts as the inducer.
  • When lactose is present, allolactose binds to and inactivates the lac repressor.
  • Inactivated repressor cannot bind to the operator, allowing RNA polymerase to transcribe the operon.
• Structural Components of the lac Operon:
  • Regulatory Gene: $lacI$.
  • Genes of Operon: $lacZ$ (codes for $\beta$-Galactosidase), $lacY$ (codes for Permease), and $lacA$ (codes for Transacetylase).

Positive Gene Regulation in Bacteria

• Catabolite Activator Protein (CAP): Some operons use positive control through stimulatory proteins like CAP, which is an activator of transcription.
• Glucose and cAMP Relationship:
  • Glucose is the preferred food source for E. coli.
  • When glucose is scarce, the concentration of cyclic AMP (cAMP) increases.
  • cAMP binds to and activates CAP.
• Transcription Acceleration:
  • Activated CAP attaches to the promoter of the lac operon.
  • This increases the affinity of RNA polymerase for the promoter, accelerating transcription.
• Transcription Deceleration:
  • When glucose levels increase, cAMP levels fall, and CAP detaches from the operon.
  • Transcription returns to a low (normal) rate even if lactose is present.

Concept 18.2: Eukaryotic Gene Expression Regulation

• Necessity of Regulation: All organisms must regulate which genes are expressed at any given time. In multicellular organisms, this is essential for cell specialization.
• Differential Gene Expression: Differences between cell types result from the expression of different genes within cells that contain the same genome.
• Implications: Abnormalities in gene expression can lead to diseases, including cancer.
• Stages of Expression Regulation:
  • Chromatin Modification: DNA unpacking.
  • Transcription: Synthesis of primary transcript.
  • RNA Processing: Addition of $5'$ Cap and $3'$ Poly-A tail; splicing of introns.
  • Transport: Movement from nucleus to cytoplasm.
  • Translation: Polypeptide synthesis on ribosomes.
  • Protein Processing: Folding, cleavage, or chemical modification.
  • Degradation: Both mRNA and proteins are eventually degraded.

Regulation of Chromatin Structure

• Structural Organization: The packing of DNA into chromatin regulates whether genes are accessible for transcription.
• Heterochromatin: Highly packed chromatin; genes within these regions are generally not expressed.
• Chemical Modifications:
  • Histone Acetylation: Acetyl groups are attached to positively charged lysines in histone tails. This loosens chromatin structure, promoting transcription initiation.
  • DNA Methylation: The addition of methyl groups to certain DNA bases (usually cytosine) is associated with reduced transcription and long-term gene inactivation (e.g., in cellular differentiation).
  • Histone Methylation: Can condense chromatin.
  • Phosphorylation: Addition of phosphate groups next to methylated amino acids can loosen chromatin.
• Epigenetic Inheritance: The inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence (like chromatin modifications) is called epigenetic inheritance. These modifications do not alter DNA sequence but can be passed to future generations of cells.
• Genomic Imprinting: Methylation regulates the expression of either the maternal or paternal alleles of specific genes at the start of development.

Regulation of Transcription Initiation in Eukaryotes

• Control Elements: Segments of noncoding DNA that serve as binding sites for transcription factors.
• Transcription Factors: Proteins required for RNA polymerase to initiate transcription.
  • General Transcription Factors: Essential for the transcription of all protein-coding genes.
  • Specific Transcription Factors: Interact with control elements to achieve high levels of transcription for particular genes.
• Types of Control Elements:
  • Proximal Control Elements: Located close to the promoter.
  • Distal Control Elements (Enhancers): May be far away from a gene, upstream or downstream, or even located within an intron.

Enhancers and Activators

• Activator Definition: A protein that binds to an enhancer and stimulates transcription.
• Activator Domains:
  • DNA-binding Domain: Attaches to the enhancer sequence.
  • Activation Domain: Interacts with other proteins (mediator proteins) to stimulate transcription.
• Transcription Initiation Complex:
  • Activators bind to distal control elements.
  • DNA-bending Protein: Brings the bound activators closer to the promoter.
  • Mediator Proteins: Facilitate interaction between activators and general transcription factors/RNA polymerase II.
• Repressors: Some transcription factors inhibit gene expression. They may act directly by blocking activator binding or indirectly by affecting chromatin structure (silencing).

Combinatorial Control and Coordinate Expression

• Combinatorial Control: A particular combination of control elements (rather than a single unique sequence) activates transcription only when the specific set of activator proteins is present.
• Coordinately Controlled Genes:
  • Unlike bacteria, co-expressed eukaryotic genes are usually not organized in operons.
  • These genes may be scattered across different chromosomes.
  • Simultaneous transcription is achieved because every gene in the group shares the same combination of control elements, which are recognized by the same set of activators.