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Understanding Regulation in Gene Expression

Apr 11, 2025

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.