Lecture Notes on Regulation and Gene Expression

Administrative Announcements

• Exam 2 is scheduled for next Monday, March 17th.
• Location issue: All students will be seated together.
• Exam details:
  • 39 multiple choice/true-false/multiple answer questions.
  • Includes one growth rate calculation question with provided formula.
  • One energetics question (no need for Gibbs free energy calculation).
  • Calculators are allowed and recommended.

Introduction to Regulation

• Specificity: Regulation is specific; for instance, lactose-related genes are regulated only in the presence of lactose.
• Global State: Regulation considers the cell's overall state (e.g., amino acid starvation stops protein synthesis regardless of glucose availability).
• Speed: Bacterial regulation is rapid, changes occur in minutes.
• Tuning: Regulation isn't binary (on/off); it's modulated based on necessity and efficiency.

General Concepts

• Allosteric Proteins:
  • Contain an active site for substrate binding and a second allosteric site for regulatory molecules.
  • Allosteric site binding can alter enzyme activity (often seen in transcriptional regulation).

Mechanisms of Regulation

• DNA structure can change gene access (common in eukaryotes, not bacteria).
• RNA Regulation: Major point in bacteria, includes initiation, elongation, termination.
• Protein Regulation: Involves translation and processing; less common focus in this class.
• Stability changes in RNA/proteins can affect translation and activity.

Negative Regulation

• Concept: Binding of a repressor decreases transcription.
• Mechanism: Repressor binds to operator, blocking RNA polymerase.
• Induction:
  • Repressor is active without inducer.
  • Inducer binds to repressor, causing it to release DNA, allowing transcription.
• Repression:
  • Repressor is inactive without co-repressor.
  • Co-repressor activates repressor, blocking transcription.

Example: Lac Operon

• Genes involved: lacZ (β-galactosidase), lacY (permease), lacA (acetyltransferase).
• Regulation:
  • LacI repressor binds operator in absence of lactose (and thus allolactose).
  • Allolactose (not lactose) is the inducer.
  • Inducer presence causes repressor to release, enabling transcription.

Positive Regulation

• Concept: Activator protein binds and increases transcription.
• Promoters: Generally weaker without activator assistance.
• Example: Maltose operon uses maltose activator protein (MalT) and co-activator (maltose).

Antisense RNA

• Function: Regulatory RNA binds to complementary mRNA, blocking translation.
• Example: SimE protein degrades mRNA, regulated by antisense RNA SimR.

Catabolite Repression

• Global Regulation: Affects multiple genes across the genome.
• Involves sensing multiple environmental signals and regulating gene expression accordingly.